Inhibitor SourceBook™ Second Edition

Inhibitor SourceBook 

Second Edition 

Your Ultimate Resource for Inhibitors 

Includes inhibitors of 

• Phosphorylation/ 

Dephosphorylation 

• Apoptosis/Necrosis 

• Cell Division/ 

Cell Cycle/ 

Cell Adhesion 

• Lipid Signaling 

• Neurobiology/ 

Neurodegeneration 

• Nitric Oxide/ 

Oxidative Stress 

• Proteases and more ...

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Calbiochem • Inhibitor SourceBook 

Inhibitor SourceBook Second Edition 

Table of Contents 

Phosphorylation/Dephosphorylation 3 

Akt (Protein Kinase B) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 

AMPK Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 

Calmodulin-Dependent Protein Kinase (CaM Kinase) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 

Casein Kinase (CK) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 

Checkpoint Kinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 

Cyclin-Dependent Kinase (Cdk) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 

DNA-Dependent Protein Kinase (DNA-PK) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 

Glycogen Synthase Kinase-3 (GSK-3) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 

c-Jun N-Terminal Kinase (JNK/SAP Kinase) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 

IP3 Kinase Inhibitor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 

Mitogen-Activated Protein (MAP) Kinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 

Myosin Light Chain Kinase (MLCK) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 

Phosphatidylinositol 3-Kinase (Pl 3-Kinase) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 

Protein Kinase A (PKA; cAMP-Dependent Protein Kinase) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 

Protein Kinase C (PKC) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 

Protein Kinase G (PKG; cGMP-Dependent Protein Kinase) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 

Protein Tyrosine Kinase (PTK) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 

Raf Kinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 

Rho Kinase (ROCK) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 

Sphingosine Kinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 

TGF-b Receptor I Kinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 

Protein Phosphatase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 

Apoptosis/Necrosis 63 

Caspase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 

Granzyme Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 

Other Inhibitors of Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 

Necrosis Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 

Cell Division/Cell Cycle/Cell Adhesion 69 

Cell Adhesion Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 

DNA Methyltransferase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 

DNA and RNA Polymerase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 

Histone Acetylase and Deacetylase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 

Nuclear Import/Export Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 

Nuclease Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 

Poly(ADP-ribose) Polymerase (PARP) and Poly(ADP-ribose) 

Glycohydrolase (PARG) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 

Telomerase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 

Topoisomerase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 

Lipid Signaling 85 

Acetyl-CoA Carboxylase (ACC) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 

Cyclooxygenase (COX) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 

Fatty Acid Hydrolase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 

Fatty Acid Synthase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 

HMG-CoA (3-Hydroxy-3-Methylglutaryl Coenzyme A) Reductase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . 89 

Lipase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 

Lipoxygenase (LOX) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 

Phospholipase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 

Sphingomyelinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 

Squalene-2, 3-oxide Cyclase Inhibitor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 

Technical Support 

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E-mail calbiochem@emdbiosciences.com

Inhibitor SourceBook Second Edition 

Table of Contents continued 

Neurobiology/Neurodegeneration 96 

Amyloidogenesis Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 

Cholinesterase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 

Monoamine Oxidase (MAO) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 

Secretase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 

Nitric Oxide/Oxidative Stress 04 

Arginase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 

Glutathione S-Transferase (GST) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 

Guanylate Cyclase (GC) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 

Nitric Oxide Synthase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 

Proteases 3 

Anthrax Lethal Factor Metalloprotease Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 

Calpain Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 

Collagenase Inhibitors (Also see Matrix Metalloproteinase Inhibitors) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 

Elastase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 

Furin Proteases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 

Matrix Metalloproteinase (MMP) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 

Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 

Protease Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 

Proteasome and Ubiquitination Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 

Other Inhibitors of Biological Interest 39 

Adenylate Cyclase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 

Angiotensin-Converting Enzyme (ACE) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 

Aromatase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 

ATPase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 

Inhibitors of Farnesyltransferase (FTase), Geranyltransferase (GGTase), and Methyltransferase . . . . . . . 144 

Inhibitors of Glycoprotein Processing and Trafficking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 

Inhibitors of Heat Shock Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 

Inhibitors of Mitochondrial Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 

NF-kB Activation Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 

Phosphodiesterase (PDE) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 

Plasminogen Activator Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 

Protein Methtyltransferase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 

Protein Synthesis Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 

Sonic Hedgehog Signaling Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 

Stem Cell Purification Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 

Tautomerase Inhibitor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 

Technical Tips/Frequently Asked Questions 64 

Indices 66 

Alphabetical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 

Numerical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172 

Trademarks, Patent, and Licensing Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 

Each product is sold with a limited warranty, which is set forth in the Terms of Sale which are provided with each purchase . 

Each product is intended to be used for research purposes only . It is not to be used for drug or diagnostic purposes nor is 

intended for human use . EMD Biosciences products may not be resold, modified for resale, or used to manufacture commercial 

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Phosphorylation/Dephosphorylation 


Akt (Protein Kinase B) Inhibitors 

Akt, also known as protein kinase B (PKB), a serine/ 

threonine kinase, is a critical enzyme in several signal 

transduction pathways involved in cell proliferation, 

apoptosis, angiogenesis, and diabetes. Four different 

isoforms of Akt (a, b1, b2, and g) have been reported 

that differ slightly in the localization of their regulatory 

phosphorylation sites. Activation of Akt involves 

growth factor binding to a receptor tyrosine kinase 

and activation of PI 3-K, which phosphorylates the 

membrane bound PI (4,5)P 2 (PIP 2 ) to generate PI(3,4,5)P 3 

(PIP 3 ). Binding of PIP 3 to Akt anchors it to the plasma 

membrane and exposes it to phosphorylation and 

activation by 3-phosphoinositide-dependent kinase-1 

(PDK1). Akt is activated following its phosphorylation 

at two regulatory residues, a threonine residue 

on the kinase domain and a serine residue on the 

hydrophobic motif, which are structurally and 

functionally conserved within the AGC kinase family. 

Phosphorylation of threonine on the kinase domain, 

catalyzed by PDK1, is essential for Akt activation. 

Akt activity is augmented approximately 10-fold by 

phosphorylation at the serine on the hydrophobic motif 

by PDK2. Phosphorylation of Thr 308 and Ser 473 activates 

Akt a. Phosphorylation at Thr 309 and Ser 474 on Akt b1 

and b2, and on Thr 305 on Akt g result in their activation. 

The activation of Akt is negatively regulated by PTEN, 

a PIP 3 specific phosphatase, and SHIP, an SH2-domain 

containing inositol 5-phosphatase. 

The principal role of Akt in the cell is to facilitate 

growth factor-mediated cell survival and to block 

apoptotic cell death. This is achieved by phosphorylating 

and deactivating pro-apoptotic factors such as BAD, 

Caspase-9, and Forkhead transcription factors (FKHR). 

The phosphorylation of BAD allows it to bind to 

14-3-3 protein thereby preventing localization of BAD 

at the mitochondria to induce apoptosis. Additionally, 

phosphorylation of FKHR by Akt prevents it from 

inducing expression of Fas ligand; hence it promotes 

cell survival. Akt also phosphorylates and activates 

IKKa, which leads to NF-kB activation and cell survival. 

Akt is also known to stimulate glycogen synthesis by 

phosphorylating and inactivating GSK-3 leading to the 

activation of glycogen synthase. The inactivation of 

GSK-3 also induces the up-regulation of cyclin D, which 

enhances cell cycle progression. Akt is reported to play 

a critical role in tumorigenesis, becoming activated 

when tumor suppressors such as p27 Kip1 and PTEN lose 

their functions. Phosphorylation of p27 at Thr 157 by Akt 

impairs its nuclear import and leads to its cytoplasmic 

accumulation. Cytoplasmic mislocalization of p27 

has been strongly linked to loss of differentiation and 

poor outcome in breast cancer patients. Akt can also 

physically associate with endogenous p21, a cell cycle 

inhibitor, and phosphorylate it at Thr 145 , causing its 

localization to the cytoplasm, ultimately resulting in 

deregulation of cell proliferation. 

References: 

Feng, J. et al. 2004. J. Biol. Chem. 279, 4 89. 

Cantley, L.C. 2002. Science 296, 655. 

Graff, J.R. 2002. Expert Opin. Ther. Targets 6, 04. 

Liang, J., et al. 2002. Nat. Med. 8, 53. 

Mitsiades, C.S., et al. 2002. Oncogene 21, 5673. 

Shiojima, I., and Walsh, K. 2002. Circ. Res. 90, 243. 

Yang, J., et al. 2002. Nat. Struct. Biol. 9, 940. 

Zhou, B.P., and Hung, M.C. 2002. Semin. Oncol. 29, 62. 

El-Deiry, W.S. 200 . Nat. Cell Biol. 3, E7 . 

Martin, D., et al. 200 . J. Neurochem. 78, 000. 

Sabbatini P., and McCormick, F. 999. J. Biol. Chem. 274, 24263. 

More online... www.calbiochem.com/inhibitors/Akt 


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3


Akt (Protein Kinase B) Inhibitors 

Product Cat. No. Comments Size Price 

Akt Inhibitor 124005 [1L-6-Hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate] 

A phosphatidylinositol ether analog that potently and selectively inhibits Akt 

(IC 50 = 5.0 mM). A weak inhibitor of phosphatidylinositol 3-kinase (IC 50 = 83 mM). 

Akt Inhibitor II 124008 (SH-5) 

A phosphatidylinositol analog that inhibits the activation of Akt and selected downstream 

substrates without affecting the phosphorylation of PDK- and other downstream kinases. 

Decreases phosphorylation of Akt without affecting the total Akt level. 

Akt Inhibitor III 124009 (SH-6) 

A phosphatidylinositol analog that inhibits the activation of Akt and selected downstream 

substrates without affecting the phosphorylation of PDK- and other downstream kinases. 

Decreases phosphorylation of Akt without affecting the total Akt level. 

mg $ 3 

mg $247 

mg $247 

Akt Inhibitor IV 124011 A cell-permeable inhibitor of Akt phosphorylation/activation that targets ATP-binding mg $95 

site of a kinase upstream of Akt, but downstream of PI 3-kinase. 

5 mg $335 

N InSolution Akt 

Inhibitor IV 

124015 A 0 mM ( mg/ 63 ml) solution of Akt Inhibitor IV (Cat. No. 240 ) in DMSO. mg $95 

N Akt Inhibitor V, 

Triciribine 

Technical Tips for use of Akt inhibitors 

Our Akt inhibitors are classified into four groups based on their modes of action. 

The first three groups of inhibitors interfere with the cellular activation of Akt and do not affect already activated Akt. These inhibitors should only be used on 

cells (with the exception of Cat. No. 240 3, which is not cell-permeable) or in coupled kinase assays, involving non-activated Akt. The fourth group of inhibitors 

is suitable for use in cell cultures, as well as in cell-free kinase assays, involving either activated or non-activated Akts. 

Group I: 

Phosphatidylinositol analogs 

(Cat. Nos. 124005/124008/ 

124009) 

These inhibitors compete with PIP 2 

thereby preventing the generation 

of PIP 3 . They also compete with PIP 3 

binding to Akt. The phosphonate 

analogs ( 24008/ 24009) display 

improved metabolic stability over 

the carbonate analog ( 24005). 

124012 (Akt/PKB Signaling Inhibitor-2; API-2; NSC 154020; TCN) 

Inhibits the cellular phosphorylation/activation of Akt /2/3 by targeting an Akt effector 

molecule other than PI 3-K or PDK . Has shown efficacy in vivo. 

N Akt Inhibitor VI, Akt-in 124013 (H-AVTDHPDRLWAWEKF-OH; TCL1 10-24 ) 

A 5-mer peptide that acts as a specific inhibitor of Akt. Shown to bind to Akt-PH 

domain (K d ~ 8 mM) and interfere with the Akt-phosphoinositide interaction. 

N Akt Inhibitor VII, 

TAT-Akt-in 

N Akt Inhibitor VIII, 

Isozyme-Selective, 

Akti- /2 

N InSolution Akt 

Inhibitor VIII, Isozyme- 

Selective, Akti- /2 

N Akt Inhibitor IX, API- 

59CJ-OMe 

Group II: 

(Cat. Nos.124011/124012/ 

124015/124019/124020/ 

252740/476880) 

These inhibitors target yet to be 

identified signaling molecules, 

other than PDK and PI 3-kinase. 

Group III: 

(Cat. Nos. 124013/124014) 

These inibitors contain a TCL - 

derived peptide inhibitor sequence, 

which binds to the PH domain of 

Akt and interferes with the Aktphosphoinositide 

interaction. 

124014 (H-YGRKKRRQRRR-AVTDHPDRLWAWEKF-OH; TAT-TCL1 10-24 ) 

A cell-permeable version of the Akt Inhibitor VI, Akt-in (Cat. No. 240 3) that directly 

binds the Akt PH domain, preventing PI binding. Has shown efficacy in vivo. 

124018 {Akti-1/2; 1,3-Dihydro-1-(1-((4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl) 

phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one} 

A cell-permeable, potent and selective inhibitor of Akt /Akt2 kinase activity 

(IC = 58 nM, 2 0 nM, and 2. 2 mM for Akt , Akt2, and Akt3, respectively. Inhibition is 

50 

PH (pleckstrin homology) domain-dependent. 

124017 A 0 mM ( mg/ 8 ml) solution of Akt Inhibitor VIII, Isozyme-Selective, Akti- /2 

(Cat. No. 240 8) in DMSO. 

124019 A cell-permeable ellipticine compound that potently and selectively inhibits cell growth 

and induces apoptosis in human endometrial cancer cells with elevated Akt levels. 

Exhibits minimal effect on cells lacking Akt activity. 

Group IV: 

(Cat. Nos. 124017/124018) 

This inhibition is pleckstrin homology 

(PH) domain-dependent. Inhibition 

is not seen in Akts lacking the PH 

domain or closely related AGC 

family kinases. This inhibitor has 

the distinct advantage of directly 

binding to either non-activated or 

activated Akt, thereby inhibiting 

both the activation of Akt and the 

kinase activity of Akt. 

mg $ 47 

2 mg $ 42 

2 mg $258 

mg $ 34 

mg $ 34 

5 mg $ 85 

4 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Akt (Protein Kinase B) Inhibitors, continued 




Akt Inhibitor X 124020 A cell-permeable inhibitor of Akt phosphorylation and its in vitro kinase activity 

(complete inhibition < 5 mM) with minimal effect on PI 3-K, PDK , and SGK . Unlike 

Akti /2 (Cat. No. 240 8), the mode of inhibition is not PH domain-dependent. 

N (-)-Deguelin, 

Mundulea sericea 

N Naltrindole, 

Hydrochloride 

AMPK Inhibitors 

252740 A cell-permeable rotenoid compound that displays antitumor properties. Selectively 

blocks Akt activation with minimal effects on MAPK signaling. Also shown to activate 

AMPK activity. 

476880 (NTI) 

A cell-permeable inhibitor of cellular Akt signaling. Decreases phosphorylation levels of 

PDK , Akt, FKHR/AFX, GSK-3b, and inhibits Akt-dependent cell growth in small cell lung 

cancer (SCLC) cell lines (IC 50 = 25, 40, and 55 mM in NCI-H69, NCI-H345, and NCI-H5 0, 

respectively). 

5 mg $20 

5 mg $67 

5 mg $84 

To view all Akt research-related 

products and to request your free 

Akt pathway wall poster, visit our 

Akt Interactive Pathways at 

www.calbiochem.com/akt 


AMPK Inhibitor, 

Compound C 

InSolution AMPK 

Inhibitor, Compound C 

Plus PI 3-kinase 

Signaling 

171260 A cell-permeable pyrrazolopyrimidine compound that acts as a potent, selective, 

reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase; K i 

= 09 nM in the presence of 5m M ATP and the absence of AMP). Does not affect the 

activities of ZAPK, Syk, PKCθ, PKA, or JAK3. Blocks cellular activities induced by AICAr 

(Cat. No. 23040) or Metformin. Induces weight loss by attenuating AMPK-mediated food 

intake in mice. 

171261 A 0 mM ( mg/250 ml) solution of AMPK inhibitor, compound C (Cat. No. 7 260) in 

DMSO. 

mg 

5 mg 

$72 

$242 

mg $72 

STO-609 570250 Significantly inhibits AMPK activation in HeLa cells (IC 50 = 0.2 mg/ml). 5 mg $ 73 


Phone 800 628 8470 


5


Calmodulin-Dependent Protein Kinase (CaM Kinase) Inhibitors 

Many effects of Ca 2+ are mediated by Ca 2+ / 

calmodulin(CaM)-dependent protein kinases 

(CaM kinases). CaM kinases constitute a family of 

structurally related enzymes that include phosphorylase 

kinase, myosin light chain kinase, and CaM kinases I-IV. 

CaM kinase II, one of the best-studied multifunctional 

enzymes, is found in high concentrations in neuronal 

synapses, and in some regions of the brain it may 

constitute up to 2% of the total protein content. 

Activation of CaM kinase II has been linked to memory 

and learning processes in the vertebrate nervous system. 

CaM kinase II is a complex of about 12 subunits that 

exist in four differentially expressed forms (a, b, g, 

and d). In the inactive state there is a strong interaction 

between the inhibitory and catalytic domains of the 

enzyme. The binding of Ca 2+ /CaM allows the catalytic 

domain to phosphorylate the inhibitory domain. Once 

activated, CaM kinase II retains significant activity 

even after the withdrawal of Ca 2+ , thereby prolonging 

the duration of kinase activity. Several synthetic and 

naturally occurring compounds have been shown 

to bind CaM in a Ca 2+ -dependent manner and block 

the activation of CaM-dependent enzymes. These 

compounds have been extensively used in investigating 

the mechanism of Ca 2+ -binding and activation in 

biological systems. 

References: 

Fujisawa, H. 2000. J. Biochem. (Tokyo) 129, 93. 

Rokolya, A., and Singer, H.A. 2000. Am. J. Physiol. 278, C537. 

Fukunaga, K., and Miyamoto, E. 999. Jap. J. Pharmacol. 79, 7. 

Kemp, B.E., et al. 994. In Protein Kinases (Woodgett, J.R., ed.), 

Oxford Univ. Press, N.Y. pp 30-67. 

ADP ATP 

More online... www.calbiochem.com/inhibitors/CAMK 

6 Orders Phone 800 854 34 7 


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Calmodulin-Dependent Protein Kinase (CaM Kinase) Inhibitors 




Autocamtide-2 Related 

Inhibitory Peptide 


Inhibitory Peptide II 


Inhibitory Peptide II, 

Cell-permeable 


Inhibitory Peptide, 

Myristoylated 

Calmodulin Binding 

Domain 

Ca 2+ /Calmodulin Kinase 

II Inhibitor 28 -309 

[Ala 286 ]-Ca 2+ / 

Calmodulin Kinase II 

Inhibitor 28 -30 

Calmodulin Kinase 

IINtide 

Calmodulin Kinase 

IINtide, Myristoylated 

189480 [(Ala 9 )-Autocamtide-2; AIP; KKALRRQEAVDAL] 

Non-phosphorylatable analog of Autocamtide-2 (Cat. No. 89475) that is a highly 

specific and potent inhibitor of CaM kinase II (IC 50 = 40 nM). 

189484 (A3K/V10F-AIP; AIP-II; KKKLRRQEAFDAL) 

An AIP-related peptide where Ala 3 and Val 0 are replaced with Lys and Phe. Highly 

specific and potent inhibitor of CaM kinase II (IC 50 = 4. nM). 

189485 (Ac-RQIKIWFQNRRMKWKKKKKLRRQEAFDAL-OH; Ant-A3K/V10F-AIP; Ant-AIP-II) 

A highly specific, potent, cell-permeable inhibitor of CaM kinase II. Contains the 

Antennapedia transport peptide sequence fused to the N-terminus of AIP-II 

(Cat. No. 89484). 

189482 (Myr-N-KKALRRQGAVDAL-OH; Myristoylated AIP) 

This peptide corresponds to AIP (Cat. No. 89480) which has been myristoylated at the 

N-terminus, enhancing its cell-permeability. 

208734 (Calmodulin antagonist; CaM kinase II 290-309) 

A potent calmodulin antagonist that inhibits the activation of CaM kinase II 

(IC 50 = 52 nM). 

208711 (CaM Kinase II Inhibitor 281-309; MHRQETVDCLKKFNARRKLKGAILTTMLA-OH) 

A synthetic peptide containing the CaM-binding domain (290-309) and the autophosphorylation 

site (Thr 286 ) of CaM kinase II. Inhibits CaM kinase II by blocking Ca 2+ / 

calmodulin activation (IC 50 = 80 nM) and enzyme-active site (IC 50 = 2 mM). 

208710 (CaM Kinase II Inhibitor 281-301; MHRQEAVDCLKKFNARRKLKG-NH 2 ) 

A synthetic peptide corresponding to residues 28 -30 of the a subunit of CaM kinase 

II that acts as a potent inhibitor (IC 50 = 2 mM) of CaM kinase II catalytic fragment. 

Inhibition is competitive with respect to ATP and in a non-competitive manner with 

respect to peptide substrate. 

208920 (KRPPKLGQIGRAKRVVIEDDRIDDVLK-OH) 

A potent and specific inhibitor of CaM kinase II (IC 50 = 50 nM). Does not affect the 

activity of CaM kinase I, IV, CaM KK, PKA, or PKC. 

208921 (Myr-N-GGGKRPPKLGQIGRAKRVVIEDDRIDDVLK-OH) 

The myristoylated, cell–permeable form of CaM Kinase IINtide (Cat. No. 208920). 

H-89, Dihydrochloride 371963 {N-[2-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl} 

A cell-permeable, selective and potent inhibitor of protein kinase A (K i = 48 nM). Inhibits 

other kinases at higher concentrations: MLCK (K i = 28.3 mM), CaM kinase II (K i = 29.7 mM), 

PKC (K i = 3 .7 mM), casein kinase I (K i = 38.3 mM), and Rho Kinase II (IC 50 = 270 nM). 

Not available for sale in Japan. 

HA 004, 

Dihydrochloride 

K-252a, Nocardiopsis 

sp. 

InSolution K-252a, 

Nocardiopsis sp. 

371964 [N-(2-Guanidinoethyl)-5-isoquinolinesulfonamide, 2HCl] 

An inhibitor of CaM kinase II (K i = 3 mM), MLCK (K i = 50 mM), PKA (K i = 2.3 mM), 

PKC (K i = 40 mM), and PKG (K i = .3 mM). Not available for sale in Japan. 

420298 A cell-permeable inhibitor of CaM kinase II (K i = .8 nM), MLCK (K i = 7 nM), protein 

kinase A (K i = 8 nM), protein kinase C (K i = 25 nM), and protein kinase G (K i = 20 nM). 

500 mg $ 9 

mg $ 06 

mg $2 7 

500 mg $ 5 

mg $ 07 

500 mg $ 6 

500 mg $208 

mg $ 07 

mg $ 7 

mg $84 

mg $57 

00 mg $ 33 

420297 A mM ( 00 mg/2 4 ml) solution of K-252a (Cat. No. 420298) in anhydrous DMSO. 00 mg $ 28 

KN-62 422706 {1-[N,O-bis-(5-Isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine} 

A cell-permeable, selective inhibitor of CaM kinase II (K i = 900 nM) that binds directly 

to the CaM-binding site of the enzyme. Not available for sale in Japan. 

KN-92 422709 {2-[N-(4-Methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, 

Phosphate} 

Useful as a negative control for KN-93 (Cat. No. 422708), a CaM kinase II inhibitor. 

KN-93 422708 {2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)- 

N-methylbenzylamine)} 

A cell-permeable, competitive inhibitor of rat brain CaM kinase II (K i = 370 nM). 

Selectively binds to the CaM-binding site of the enzyme and prevents the association of 

CaM with CaM kinase II. 

mg $ 03 

mg $ 03 

KN-93, Water-Soluble 422711 A water-soluble form of the CaM kinase II inhibitor KN-93 (Cat. No. 422708). mg $ 03 

InSolution KN-93 422712 A 5 mM ( mg/399 ml) solution of KN-93 Inhibitor (Cat. No. 422708) in DMSO. mg $ 09 

mg 

5 mg 

$ 03 

$36 


Phone 800 628 8470 


7


Calmodulin-Dependent Protein Kinase (CaM Kinase) Inhibitors, continued 


Lavendustin C 234450 [Compound 5; 5-(N-2´,5´-Dihydroxybenzyl)aminosalicylic Acid] 

Potent inhibitor of CaM kinase II (IC 50 = 200 nM) and pp60 c-src (IC 50 = 200 nM). 

N PP Analog II, 

NM-PP 

529581 A cell-permeable PP analog (Cat. No. 529579) that acts as a potent and selective ATPcompetitive 

inhibitor of a variety of mutant kinases over wild-type (IC 50 = 3.2 nM for 

T339G, c-Fyn-as vs. .0 mM for c-Fyn; 4.3 nM for I338G, v-src-as vs. 28 mM for v-src; 

5 nM for F80G, CDK2-as vs. 29 mM for CDK2; 8 nM for F89G, CAMK IIa-as vs. 

24 mM for CAMKII; 20 nM for T3 5A, c-Abl-as2 vs. 3.4 mM for c-Abl). Shown to 

activate mutants of Ire , a transmembrane kinase. 

STO-609 570250 A cell-permeable, highly selective, potent, ATP-competitive inhibitor of CaM kinase kinase 

(CaM-KK) (IC 50 = 320 nM and 06 nM for CaM-KKa and CaM-KKb isoforms, respectively). 

Binds to the catalytic domain of CaM-KK, and inhibits autophosphorylation. 

TX-1918 

A cell-permeable, potent inhibitor for eEF2 kinase (IC 50 = 440 nM). 

Inhibits other kinases at much higher concentrations (IC 50 = 4.4, 44, 44, 

and 440 mM for Src, PKA, PKC, and EGFR kinase, respectively). 

Cat. No. 655203 10 mg $90 

Including Oncogene 

Research Products 

mg $62 

mg $82 

5 mg $ 73 

Featuring 50 

NEW products 

8 Orders Phone 800 854 34 7 


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Casein Kinase (CK) Inhibitors 

Casein kinases I and II (CKI and CKII) are highly 

conserved, ubiquitous serine/threonine protein kinases 

that play a significant role in neoplasia and cell survival. 

CKI can be found in the nucleus and the cytosol and 

is bound to the cytoskeleton and membranes. The CKI 

family consists of several isoforms (CKIa, b, g1, g2, 

g3, d, and e) encoded by seven distinct genes. It plays a 

significant role in the regulation of circadian rhythm, 

intracellular trafficking and also acts as a regulator of 

Wnt signaling, nuclear import, and the progression of 

Casein Kinase (CK) Inhibitors 



Alzheimer’s disease. CKII has traditionally been classified 

as a messenger-independent protein serine/threonine 

kinase and consists of two catalytic and two regulatory 

subunits. It plays an important role in the progression 

of the cell cycle and in maintenance of cell viability. 

It is highly conserved and is known to phosphorylate 

about 300 different proteins. CKII activity is required at 

transition points of the cell cycle. Excessive activity of 

CKII has been linked to oncogenic transformation and the 

development of primary and metastatic tumors. 


A3, Hydrochloride 100122 [N-(2-Aminoethyl)-5-chloronaphthalene-1-sulfonamide, HCl] 

A shorter alkyl chain derivative of W-7 (Cat. No. 68 629) that inhibits CKI (K i = 80 mM), CKII 

(K i = 5. mM), MLCK (K i = 7.4 mM), PKA (K i = 4.3 mM), PKC (K i = 47 mM), and PKG (K i = 3.8 mM). 

N Casein Kinase I 

Inhibitor, D4476 

N InSolution Casein 

Kinase I Inhibitor, D4476 

Casein Kinase II 

Inhibitor I 


Kinase II Inhibitor I 

N Casein Kinase II 

Inhibitor II, DMAT 


Kinase II Inhibitor, 

DMAT 

218696 {CKI Inhibitor; 4-(4-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol- 

2-yl)benzamide} 

A cell-permeable, potent, and relatively specific ATP-competitive inhibitor of CKI 

(IC 50 = 200 nM from S. pombe; 300 nM for CKId). Shown to be ~ 0-fold more potent 

than IC26 (Cat. No. 400090; IC 50 = 2.5 mM for CKI). 

218705 A 0 mM ( mg/25 ml) solution of Casein Kinase I Inhibitor, D4476 


218697 (CKII Inhibitor; TBB; TBBt; 4,5,6,7-Tetrabromo-2-azabenzimidazole; 4,5,6,7- 

Tetrabromobenzotriazole) 

A cell-permeable, highly selective, ATP/GTP-competitive CKII inhibitor 

(IC 50 = 900 nM and .6 mM for rat liver and human recombinant CKII, respectively 

and DYRK (IC 50 < mM for DYRK a). 

218708 A 0 mM (5 mg/ . 5 ml) solution of Casein Kinase II Inhibitor I 


218699 (CKII Inhibitor II, DMAT; 2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) 

A cell-permeable, potent, high affinity and ATP-competitive inhibitor of CKII (IC 50 = 40 nM 

rat liver; K i = 40 nM). Displays ~ 300 fold greater selectivity over CKI (IC 50 > 200 mM) and is 

superior to CKII inhibitor, TBB (Cat. No. 2 8697). 

218706 A 0 mM (5 mg/ .05 ml) solution of Casein Kinase II Inhibitor, DMAT 

(Cat. No. 2 8699), in DMSO. 

Daidzein 251600 (4´,7-Dihydroxyisoflavone) 

Inactive analog of Genistein that is reported to inhibit casein kinase II activity. 

5,6-Dichloro- -b-Dribofuranosylbenz– 

imidazole 

287891 (5,6-Dichlorobenzimidazole Riboside; DRB) 

Potent and specific inhibitor of casein kinase II (IC 50 = 6 mM). 

Ellagic Acid, Dihydrate 324683 4,4′,5,5′,6,6′-Hexahydroxydiphenic Acid 2,6,2′,6′-Dilactone 

A cell-permeable, potent, selective and ATP-competitive inhibitor of CKII (IC 50 = 40 nM). 


A cell-permeable, selective and potent inhibitor of PKA (K i = 48 nM). At higher 

concentrations it also inhibits MLCK (K i = 28.3 mM), CaM kinase II (K i = 29.7 mM), 

PKC (K i = 3 .7 mM), CKI (K i = 38.3 mM), and Rho kinase II (IC 50 = 270 nM). 


InSolution H-89, 


More online... www.calbiochem.com/inhibitors/CK 

371962 N-[2-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl 

A 0 mM ( mg/ 93 µl) solution of H-89, Dihydrochloride (Cat. No. 37 963) in DMSO. 


Key: CKI: Casein kinase I; CKII: Casein kinase II; MLCK: Myosin light chain kinase; PKA: Protein kinase A; PKC: Protein kinase C 

0 mg $90 

mg $ 2 

mg $ 2 

0 mg $73 

5 mg $53 

5 mg $90 

5 mg $90 

25 mg $47 

50 mg $90 

500 mg $57 

mg $84 

mg $84 


Phone 800 628 8470 


9


Casein Kinase (CK) Inhibitors, continued 


Hypericin 400076 A potent inhibitor of CKII (IC 50 = 6 nM). Also inhibits PKC (IC 50 = 3.3 mM), MAP kinase 

(IC 50 = 4 nM), and the protein tyrosine kinase activity of the insulin receptor 

(IC 50 = 20–29 nM) and the EGF receptor (IC 50 = 35 nM). 

IC26 400090 {3-[(2,4,6-Trimethoxyphenyl)methylidenyl]-indolin-2-one} 

A potent and selective inhibitor of CKId (IC 50 = 0.7 - .3 mM) and CKIe 

(IC 50 = 0.6– .4 mM). Also inhibits CKIa at much higher concentrations 

(IC 50 = –2 mM). The inhibition is competitive with respect to ATP. 

 

 

 

Includes 

Non-detergent 

Sulfobetaines 

iFOLD 

Protein Refolding System 

Inclusion body preparation and a 96-well matrix of buffers 

and additives for convenient optimization of refolding conditions 

Request your FREE copy today! 

Now Available Refold 

recombinant 

proteins 

mg $ 05 

5 mg $ 2 

0 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Checkpoint Kinase Inhibitors 

Eukaryotes have evolved elaborate sensory networks to 

detect and repair DNA damage and prevent alterations 

in their genetic material. In response to DNA damage, 

eukaryotic cells arrest either in G1 or S phase, to prevent 

replication of damaged genes, or in G2 phase to avoid 

segregation of defective chromosomes. Checkpoint 

kinases, Chk1 and Chk2, participate in various DNAdamage 

responses, including cell-cycle checkpoints, 

genome maintenance, DNA repair, and apoptosis. They 

phosphorylate several key proteins involved in cell cycle 

and block their activity. 

Chk1, an evolutionarily conserved protein kinase, 

is expressed in the S and G2 phases of cell cycle of 

proliferating cells. It is activated by phosphorylation 

of Ser 317 and Ser 345 in response to DNA damage. Once 

activated, Chk1 phosphorylates Ser 123 of Cdc25A, 

which targets it for ubiquitin-mediated degradation. 

The phosphorylated Cdc25A cannot dephosphorylate 

and activate Cdk1 and Cdk2, resulting in an arrest 

of cell cycle in the G1, S, and G2 phases. Chk1 

also phosphorylates Ser 216 on Cdc25C and prevents 

its activation in the G2 phase. Phosphorylated 

Cdc25C cannot dephosphorylate and activate Cdk1. 

Recent research indicates that Chk1 is an ideal 

chemosensitization target and its inhibition can sensitize 

tumors, particularly those with p53-deficiency, to 

various chemotherapeutic agents. 

Chk2 is structurally different from Chk1, but they share 

overlapping substrate specificities. Chk2 is activated 

following exposure to infrared light or topotecan, 

whereas Chk1 is activated by agents that interfere 

with DNA replication. This observation has lead to the 

belief that Chk1 blocks cell-cycle progression when 

replication is inhibited, whereas Chk2 acts when there 

are double-strand breaks. Chk2 is activated by DNAstrand-breaking 

agents such as ionizing radiation 

and topoisomerase inhibitors through the ATMdependent 

pathway. The role of Chk2 in checkpoints 

is not clearly understood. However, it is reported to 

phosphorylate Cdc25A and inhibit its activity. Chk2 also 

phosphorylates Ser 20 at the amino-terminal activation 

domain of p53 and regulates levels of p53 in response to 

DNA double strand breaks. However, phosphorylation 

of Ser 20 is not the only important event for p53 response 

induced by UV light. Chk2 can also regulate p53 through 

targeting several other phosphorylation sites. 



Many current cancer treatments, including certain 

classes of chemotherapeutics, induce cytotoxicity 

by damaging DNA. However, many cancers become 

resistant to these therapies. Thus, modulating DNAdamage 

responses to selectively enhance the sensitivity 

of cancer cells to these therapies is highly desirable. 

Inhibitors of Chk1 and Chk2 have shown potential 

to enhance the efficacy of DNA-damaging cancer 

therapeutic agents by selectively increasing the 

sensitivity of tumor cells. 

References: 

Sorenson, C.S., et al. 2005. Nat. Cell Biol. 7, 95. 

Zhou, B.B.S. and Bartek, J. 2004. Nat. Rev. Cancer 4, 2 6. 

Craig, A., et al. 2003. EMBO Rep. 4, 787. 

O’Neill, T., et al. 2002. J. Biol. Chem. 277, 6 02. 

Zhao, H., et al. 2002. Proc. Natl. Acad. Sci. USA 99, 4795. 

Graves, P.R., et al. 2000. J. Biol. Chem. 275, 5600. 

Hirao, A., et al. 2000. Science 287, 824. 

Mailand, N., et al. 2000. Science 288, 425. 

Zhou, B-B., et al. 2000. Nature 408, 433. 

More online... www.calbiochem.com/inhibitors/checkpoint 


Phone 800 628 8470 



Checkpoint Inhibitors 


N Chk2 Inhibitor 220485 {5-(2-Amino-5-oxo-1,5-dihydroimidazol-4-ylidine)-3,4,5,10-2H-azepino[3,4-b] 

indol-1-one, HCl} 

A cell-permeable, potent inhibitor of Chk2 (IC 50 = 8 nM) with good selectivity over 

MEK , Chk , CKId, PKCa, PKCbII, and CKII (IC 50 = 89 nM, 237 nM, .352 mM, 2.539 mM, 

3.38 mM, and > 0.0 mM, respectively). 

N Chk2 Inhibitor II 220486 [2-(4-(4-Chlorophenoxy)phenyl)-1H-benzimidazole-5-carboxamide] 

A cell-permeable, potent, ATP-competitive inhibitor of Chk2 with an IC 50 of 5 nM and a 

K i of 37 nM. Displays ~ 000-fold greater selectivity over Cdk /B and CKI (IC 50 = 2 mM 

and 7 mM) and weakly affects the activities of a panel of 3 kinases ( < 25% inhibition 

at 0 mM), including Chk . 

Debromohymenialdisine, 

Stylotella aurantium 

252010 (DBH) 

An alkaloid isolated from a shallow-water marine sponge that acts as a highly selective 

inhibitor of checkpoint kinases Chk (IC 50 = 3 mM) and Chk2 (IC 50 = 3.5 mM). Inhibition is 

competitive with respect to ATP and does not affect the activities of other kinases. 

N Isogranulatimide 371957 (IGR) 

A cell-permeable, potent, and ATP-competitive inhibitor of Chk (IC = 00 nM) and 

50 

GSK-3b (IC = 500 nM). Displays selectivity over G DNA damage checkpoint, Chk2, 

50 2 

Cdk , and DNA-PK (IC = 3 mM, 4 mM, 0 mM, and 0 mM, respectively). Only minimally 

50 

affects the activities of several other kinases tested including PKA, PKBa, and PKCb 

(IC ≥ 40 mM). 

50 

N SB 2 8078 559402 [9,10,11,12,-Tetrahydro-9,12-epoxy-1H-diindolo(1,2,3-fg:3´,2´,1´-kl)pyrrolo 

(3,4-i)(1,6)benzodiazocine-1,3(2H)-dione] 

An indolocarbazole derivative that acts as a potent and selective inhibitor of checkpoint 

kinase (Chk ) in vitro. Inhibits Chk phosphorylation of Cdc25C (IC = 5 nM). 

50 

SB-2 8078 is a much weaker inhibitor of Cdc2 (IC = 250 nM) and PKC (IC = mM). 

50 50 

N Scytonemin, Lyngbya 

sp. 

565715 A cell-permeable, selective, reversible, non-toxic, and mixed type inhibitor of polo-like 

kinase (Plk ; IC 50 = 2.0 mM) and PKC bI (IC 50 = 3.4 mM) and exhibits anti-proliferative 

and anti-inflammatory properties. Also inhibits several other cell cycle regulatory 

kinases (IC 50 = 2.7, 3.0, .2, and .4 mM respectively for PKC bII , Cdk /B, Mytl, and Chk ). 

To view all Checkpoint Signaling and DNA Repair research-related 

products and to request your free wall poster, visit our 

Checkpoint Signaling and DNA Repair Interactive Pathways at: 

www.calbiochem.com/checkpoint 

500 mg $ 96 

mg $93 

00 mg $98 

mg $ 39 

mg $ 06 

mg $98 

2 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Cyclin-Dependent Kinase (Cdk) Inhibitors 

Cell cycle progression is regulated by a series of 

sequential events that include the activation and 

subsequent inactivation of cyclin dependent kinases 

(Cdks) and cyclins. Cdks are a group of serine/threonine 

kinases that form active heterodimeric complexes by 

binding to their regulatory subunits, cyclins. Eleven 

members of the Cdk family are reported so far, and each 

member of the family has a specific function in cellcycle. 

Several Cdks, mainly Cdk2, Cdk4, and Cdk6, work 

cooperatively to drive cells from G 1 phase into S phase. 

Cdk4 and Cdk6 are involved in early G 1 phase, whereas 

Cdk2 is required to complete G 1 phase and initiate S 

phase. Both Cdk4 and Cdk6 form active complexes with 

the D type of cyclins (cyclins D1, D2, and D3). Cdk2 is 

sequentially activated by the E type of cyclins, cyclins 

E1 and E2, during G 1 /S transition stage. A-type cyclins, 

cyclin A1 and A2, play a role during S phase. Cdk2/cyclin 

A complex appears during late S phase and plays a role 

in progression of DNA replication. The cyclins that are 

involved in regulating the passage of the cell from the G 2 

checkpoint into M phase are known as mitotic cyclins and 

they associate with mitotic Cdks. Similarly, cyclins that 

are involved in the passage of cells from the G 1 checkpoint 

into S phase are called G 1 cyclins. Once the Cdks have 

completed their role, they undergo a rapid programmed 

proteolysis via ubiquitin-mediated delivery to the 

proteasome complex. 

It is important to note here that Cdk5, a serine-threonine 

kinase, originally cloned from HeLa cells, is not directly 

involved in cell cycle. It is primarily active in neuronal 

Cyclin B 

Cdk1 

Cdk1 

Cyclin B 

Cyclin A 

Cdk1 


H 

E2F 

E2F 

Cdk2 

E2F 

Cyclin A 

Cdk4 

Cyclin D 

Cdk2 


tissue. Cdk5, in conjunction with its neuron-specific 

activator p35 (Cdk5/p35), has been implicated in tau 

hyperphosphorylation. Cdk5/p35 is also involved 

in neuronal migration and differentiation during 

development of the nervous system. 

The enzymatic activity of a Cdk is regulated at three 

levels: cyclin association, subunit phosphorylation, and 

association with Cdk inhibitors. When cyclins initially 

bind to Cdks, the resulting complex is inactive. The 

phosphorylation of Cdks by Cdk activating kinases leads 

to their activation. Two main categories of Cdk inhibitors 

are reported in cells. They are the INK and the WAF/Kip 

families. The members of the INK family, INK4A (p16), 

INK4B (p15), INK4C (p18), and INK4D (p19), bind to Cdk4 

and Cdk6 and block their interaction with D type cyclins 

thereby inhibiting Cdk activity. The members of the 

WAF/Kip family, WAF1 (p21), Kip1 (p27), and Kip2 (p57), 

form heterotrimeric complexes with the G 1 /S Cdks. Their 

major action is reported to be the inhibition of the kinase 

activity of Cdk/cyclin E complex. From a therapeutic 

standpoint, Cdks are considered promising targets in 

cancer chemotherapy. The most promising strategies 

involve designing inhibitors that either block Cdk activity 

or prevent their interaction with cyclins. Most of the 

currently available molecules target the ATP-binding site 

of these enzymes. Such an approach might create serious 

problems as catalytic residues are well conserved across 

eukaryotic protein kinases. However, compounds such 

as Flavopiridol, Olomoucine, and Butyrolactone-1 that 

exhibit greater specificity for Cdks have shown promise. 

Cyclin E 

References: 

Sridhar, J. et al. 2006. AAPS J. 8, E204. 

Murray, A.W. 2004. Cell 116, 22 . 

Fischer, P.M., et al. 2003. Prog. Cell Cycle Res. 5, 235. 

Dai, Y., and Grant, S. 2003. Curr. Opin. Pharmacol. 3, 362. 

Harper, J.W., and Adams, P.D. 200 . Chem. Rev. 101, 25 . 

Ekholm, S.V., and Reed, S.I. 2000. Curr. Opin. Cell Biol. 12, 676. 

More online... www.calbiochem.com/inhibitors/Cdk 


Phone 800 628 8470 


3


Selected Cdk Inhibitors (IC 50 in mM) 

Product Cat. No. Cdk1 Cdk2 Cdk4 Cdk5 

Alsterpaullone 26870 0.035 – – – 

Alsterpaullone, 2-Cyanoethyl 2687 0.000230 – 0.030 

Aloisine A 28 25 0. 5 (B) 0. 2 (A), 0.40 (E) 0.20 (p25), 0. 6 (p35) 

Aloisine A, RP 06 28 35 0.70 (B) .50 (p35) 

N Aminopurvalanol A 64640 0.033 0.033 (A), 0.028 (E) 0.020 (p35) 

Bohemine 203600 .0 0.80 (E) – – 

Cdk Inhibitor, p35 2 9457 0. 0 0.80 (E) – – 

Cdk Inhibitor 2 7695 5.8 – – 25.0 

Cdk Inhibitor, CGP745 4A 2 7696 0.025 (B) – – – 

Cdk Inhibitor III 2 7697 28.8 (B) – – – 

N Cdk /2 Inhibitor II, NU6 02 2 77 3 0.0095 (B) 0.0054 (A3) .6 (D ) – 

Cdk /5 Inhibitor 2 7720 0.60 (B) – – 0.40 (p25) 

Cdk2 Inhibitor I 2 9442 – 0.038 a – – 

Cdk2 Inhibitor II 2 9445 0.78 0.060 – – 

Cdk2 Inhibitor III 238803 4.2 (B) 0.5 (A and E) 2 5.0 (D ) – 

Cdk2/5 Inhibitor 2 9448 – 2.0 b – 2.0 b 

N Cdk4 Inhibitor 2 9476 2. (B) 0.52 (E) 0.076 (D ) – 

N Cdk4 Inhibitor II, NSC 625987 2 9477 > 00 (A) > 00 (E) 0.20 (D ) – 

Fascaplysin, Synthetic 34 25 > 00 > 50 (A and E) 0.35 (D ) 20.0 

Hymenialdisine, Stylissa damicornis 400085 0.022 0.040 (E) 0.028 

Indirubin-3’-monoxime 402085 0. 8 - - 0. 0 

Indirubin-3’-monoxime, 5-Iodo- 402086 0.025 - - 0.020 

Indirubin-3’-monoxime-5-sulphonic Acid 402088 0.005 - - 0.007 

Kenpaullone 422000 0.40 (B) 0.68 (A), 7.5 (E) - 0.85 

Olomoucine 495620 7.0 (B) 7.0 (A and E) > 000 (D) 3.0 (p35) 

Olomoucine II 49562 0.02 (B) 

Olomoucine, Iso 495622 > 500 (B) > 000 (D) > 000 (p35) 

Olomoucine, N 9 -Isopropyl- 495623 2.0 

Oxindole I 499600 0.2 0.0 (E) 4.90 

Protein Kinase inhibitor, DMAP 476493 300 (B) 

Purvalanol A 540500 0.004 (B) 0.07 (A), 0.035 (E) 0.075 (p35) 

Roscovitine 557360 0.65 0.7 (A and E) > 000 0.2 (p35) 

Roscovitine, (S)-Isomer 557362 0.80 (B) 

Staurosporine 569397 0.009 0.007 - - 

SU95 6 572650 0.04 (B) 0.022 (A) 0.20 (D ) 

WHI-P 80, Hydrochloride 68 500 .0 

Key: a = K d ; b = K i . Letters in parentheses refer to associated cyclins or Cdks. 

4 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Cyclin-Dependent Kinase (Cdk) Inhibitors 




Aloisine A 128125 {7-n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP107} 

A potent, cell-permeable, selective, reversible, and ATP-competitive inhibitor of Cdks 

(IC 50 = 50 nM for Cdk /cyclin B, 20 nM for Cdk2/cyclin A, 400 nM for Cdk2/cyclin E, 

and 60 nM for Cdk5/p35). Also inhibits GSK-3 (IC 50 = 500 nM for GSK-3a and .5 mM 

for GSK-3b), JNK (IC 50 ~3– 0 mM), ERKs (IC 50 = 8 mM for ERK and 22 mM for ERK2), 

PIM (IC 50 > 0 mM), and insulin receptor tyrosine kinase (IC 50 = 60 mM). 

Aloisine, RP 06 128135 {7-n-Butyl-6-(4-methoxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP106} 

A cell-permeable, potent, selective, ATP-competitive inhibitor of Cdk /cyclin B 

(IC 50 = 700 nM), Cdk5/p25 (IC 50 = .5 mM), and GSK-3 (IC 50 = 920 nM). 

Alsterpaullone 126870 {9-Nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one} 

A potent inhibitor of Cdk /cyclin B (IC 50 = 35 nM). Also inhibits the activity of Cdk5/p25dependent 

phosphorylation of DARPP-32. One of the most active paullones that acts by 

competing with ATP for binding to GSK-3b and inhibits the phosphorylation of tau. 

N Alsterpaullone, 

2-Cyanoethyl 

126871 An Alsterpaullone (Cat. No. 26870) derivative that acts as a highly potent and ATPcompetitive 

preferential inhibitor of Cdk /B and GSK-3b (IC 50 = 230 pM and 800 pM, 

respectively; [ATP] = 5 mM), and displays ~37-fold greater selectivity over Cdk5/p25 

(IC 50 = 30 nM). Shown to inhibit other kinases in a commercially available testing screen 

panel (pIC 50 = -logIC 50 [M]; pIC 50 ~ 7.5, 7.0, 7.0, 6.5, 6.5, 6.0, and 6.0 for Cdk2/A, Cdk4/D , 

GSK-3b, PDGFRb, Src, VEGFR-2, and VEGFR-3, respectively; [ATP] = mM). 

N Aminopurvalanol A 164640 [(2R)-2-((6-((3-Amino-5-chlorophenyl)amino)-9-(1-methylethyl)-9H-purin-2-yl)amino)- 

3-methyl-1-butanol; NG-97] 

A cell-permeable, 2,6,9-trisubstituted purine analog with antitumor properties 

(GI 50 ~ .8 mM in the NCI 60-cell panel in vitro activity screen, potently inhibits the 

growth of KM 2 colon cancer cells with a GI 50 of 30 nM). Acts as a reversible and ATPcompetitive 

inhibitor of Cdks (IC 50 = 33 nM for Cdk /cyclin B and Cdk2/cyclin A, 28 nM 

for Cdk2/cyclin E, and 20 nM for Cdk5/p35), and displays ~ 00-fold greater selectivity 

over a panel of kinases tested (IC 50 ≥ 2.4 mM). 

Bohemine 203600 {[6-Benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine} 

A synthetic, cell-permeable, Cdk inhibitor (IC 50 = mM) that is structurally similar to 

Olomoucine (Cat. No. 495620) and Roscovitine (Cat. No. 557360). 

N Cdc2-Like Kinase 

Inhibitor, TG003 

219479 [Clk Inhibitor, TG003; (Z)-1-(3-Ethyl-5-methoxy-2,3-dihydrobenzothiazol- 

2-ylidene)propan-2-one] 

A cell-permeable dihydrobenzothiazolo compound that acts as a potent, specific, 

reversible, and ATP-competitive inhibitor of Clk-family of kinases (K i = 0 nM for mClk / 

Sty; IC 50 = 5 nM, 20 nM, 200 nM, and > 0 mM for mClk4, mClk , mClk2, and mClk3, 

respectively). Does not affect the activities of SRPK , SRPK2, PKA, or PKC up to mM. 

Cdk Inhibitor, p35 219457 [2-(3-Hydroxypropylamino)-6-(o-hydroxybenzylamino)-9-isopropylpurine] 

An analog of Olomoucine (Cat. No. 495620) that acts as a potent inhibitor of Cdk 

(IC 50 = 00 nM) and Cdk2 (IC 50 = 80 nM). 

Cdk Inhibitor 217695 [3-(2-Chloro-3-indolylmethylene)-1,3-dihydroindol-2-one] 

A selective, ATP-competitive inhibitor of Cdk /cyclin B (IC 50 = 5.8 mM for Cdk and 

25 mM for Cdk5). Does not affect the activity of GSK-3b even at 00 mM 

concentrations. Binds to the ATP pocket in the Cdk active site. 

Cdk Inhibitor, 

CGP745 4A 

217696 [N-(cis-2-Aminocyclohexyl)-N-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine; 

CGP74514A] 

A cell-permeable, potent, and selective inhibitor of Cdk /cyclin B (IC = 25 nM). 

50 

Cdk Inhibitor III 217697 {Ethyl-(6-hydroxy-4-phenylbenzo[4,5]furo[2,3-b])pyridine-3-carboxylate} 

A cell-permeable and selective inhibitor of Cdk /cyclin B (IC 50 = 28.8 mM). 

N Cdk /2 Inhibitor II, 

NU6 02 

217713 [6-Cyclohexylmethoxy-2-(4´-sulfamoylanilino)purine] 

A 2,6-disubstituted purine compound that acts as a potent and ATP-competitive 

inhibitor of Cdk /cyclin B and Cdk2/cyclin A3 (IC 50 = 9.5 nM and 5.4 nM). Displays greater 

selectivity for Cdk /2 over other kinases tested (IC 50 = 600 nM, 800 nM, 900 nM, and 

.6 mM for ROCKII, PDK , DYRK A and Cdk4/D , respectively). Shown to inhibit human 

MCF-7 breast carcinoma cell growth with a GI 50 of 8 mM. 

5 mg $90 

5 mg $73 

mg $83 

mg $ 39 

5 mg $ 52 

mg 

5 mg 

$60 

$ 46 

5 mg $84 

mg $72 

5 mg $ 0 

5 mg $ 26 

mg 

5 mg 

mg 

5 mg 

$84 

$299 

$57 

$ 45 


Phone 800 628 8470 


5


Cyclin-Dependent Kinase (Cdk) Inhibitors, continued 


N Cdk /2 Inhibitor III 217714 A cell-permeable triazolo-diamine compound that displays anti-proliferative properties 

in various human cancer cells (IC 50 = 20 nM, 35 nM and 92 nM in HCT- 6, HeLa and A375 

cells, respectively). Acts as a highly potent ATP-competitive inhibitor of Cdk /B and Cdk2/ 

A (IC 50 = 600 pM and 500 pM) with selectivity over VEGF-R2 and GSK-3b 

(IC 50 = 32 nM and 40 nM). Only minimally affects a panel of kinases tested (IC 50 = .0 mM, 

.6 mM, 2.8 mM, 5.2 mM, 8.9 mM, > 0 mM, and > 00 mM for ERK-2, PDGF-Rb, CKI, PKA, 

CaMKII, EGF-R or insulin kinase-b, and CKII, respectively). 

Cdk /5 Inhibitor 217720 (3-Amino-1H-pyrazolo[3,4-b]quinoxaline) 

A selective and potent inhibitor of Cdk and Cdk5 (IC 50 = 600 nM for Cdk /cyclin B and 

400 nM for Cdk5/p25 respectively). 

Cdk2 Inhibitor I 219442 (YSFVHHGFFNFRVSWREMLA) 

A potent inhibitor of Cdk2 (K d = 38 nM). 

Cdk2 Inhibitor II 219445 (Compound 3) 

A potent and selective inhibitor of Cdk2 (IC 50 = 60 nM). 

Cdk2 Inhibitor III 238803 [2(bis-(Hydroxyethyl)amino)-6-(4-methoxybenzylamino)-9-isopropyl-purine] 

A cell-permeable, selective, reversible, ATP-competitive inhibitor of Cdk2/cyclin A and 

Cdk2/cyclin E (IC 50 = 500 nM). 

N Cdk2 Inhibitor IV, 

NU6 40 

238804 A highly cell-permeable purine compound that acts as a selective and ATP-competitive 

inhibitor of Cdks (IC 50 = 6.6 mM, 0.4 mM, 5.5 mM, 5 mM, and 3.9 mM for Cdk /B, Cdk2/ 

A, Cdk4/D, Cdk5/p25, and Cdk7/H, respectively), and displays anticancer properties. 

Shown to cause cell cycle arrest at G 2 -M phase, and induce apoptosis by activating 

caspases and downregulating survivin. Further, synergistically potentiates paclitaxel 

cytotoxicity and apoptotic response in HeLa, OAW42/e, and OAW42/Surv cells. 

Cdk2/5 Inhibitor 219448 [N 4 -(6-Aminopyrimidin-4-yl)-sulfanilamide, HCI; PNU 112455A] 

An aminopyrimidine derivative that acts as a selective inhibitor of Cdk2/cyclin E and 

Cdk5/p25 (K i = 2 mM). The inhibition is competitive with respect to ATP. 

Cdk2/Cyclin Inhibitory 

Peptide I 

Cdk2/Cyclin Inhibitory 

Peptide II 

238801 (Tat-LFG; YGRKKRRQRRRGPVKRRLFG) 

A cell-permeable peptide inhibitor derived from the consensus sequence, PVKRRLFG, 

that serves as the docking site for Cdk2/cyclin complexes. Blocks the phosphorylation of 

substrates by Cdk2/cyclin A and Cdk2/cyclin E complexes. 

238802 (Tat-LDL; YGRKKRRQRRRGPVKRRLDL) 

A cell-permeable peptide inhibitor derived from the cell-cycle regulatory transcription 

factor, E2F, that is derived from the Cdk2/cyclin A binding motif. Blocks the 

phosphorylation of substrates by Cdk2/cyclin A and Cdk2/cyclin E complexes. 

Cdk4 Inhibitor 219476 {2-Bromo-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione} 

A cell-permeable, potent, selective ATP-competitive inhibitor of Cdk4/cyclin D 

(IC 50 = 76 nM). 

N Cdk4 Inhibitor II, NSC 

625987 

219477 [1,4-Dimethoxy-9-thio(10H)-acridone] 

A potent, substrate-competitive inhibitor of Cdk4/cyclin D (IC 50 = 200 nM). Displays 

~500-fold greater selectivity for Cdk4/cyclin D over Cdc2/cyclin A (Cdk /cyclin A), 

Cdk2/cyclin A, and Cdk2/cyclin E (IC 50 > 00 mM). 

Compound 52 234503 [2-(2-Hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine] 

A potent, cell-permeable, and selective inhibitor of the cell cycle-regulating kinase, 

Cdc28p (IC 50 = 7 mM), and the related Pho85p kinase (IC 50 = 2 mM). 

mg $88 

5 mg $ 8 

mg $ 23 

6 Orders Phone 800 854 34 7 


Fax 800 776 0999 

Web www.emdbiosciences.com/calbiochem 

mg 

5 mg 

mg 

5 mg 

$39 

$ 23 

$58 

$200 

5 mg $ 39 

5 mg $93 

500 mg $ 0 

500 mg $ 0 

mg $84 

5 mg $ 8 

mg $65 

Fascaplysin, Synthetic 341251 A cell-permeable, potent, ATP-competitive inhibitor of Cdk4/cyclin D (IC 50 = 350 nM). mg $79 

GSK-3 Inhibitor IX 361550 BIO; (2'Z,3'E)-6-Bromoindirubin-3'-oxime 

A cell-permeable, highly potent, selective, reversible, and ATP-competitive inhibitor of 

GSK-3a/b (IC 50 = 5 nM). At higher concentrations, inhibits Cdk2/cyclin A (IC 50 = 300 nM) 

and Cdk5/p25 (IC 50 = 83 nM). 

InSolution GSK-3 

Inhibitor IX 

Hymenialdisine, Stylissa 

damicornis 

mg $95 

361552 A 0 mM (500 mg/ 40 ml) solution of GSK-3 Inhibitor IX (Cat. No. 36 550) in DMSO. 500 mg $63 

400085 {4-(2-Amino-4-oxo-2-imidazolidin-5-ylidene)-2-bromo-4,5,6,7-tetrahydropyrrolo 

2,3-c]azepin-8-one; HD; 10Z-Hymenialdisine} 

A cell-permeable, ATP-competitive inhibitor of MEK- (IC = 6 nM), Cdk /cyclin B 

50 

(IC = 22 nM); Cdk2/cyclin E (IC = 40 nM); Cdk5/p35 (IC = 28 nM); and GSK-3b 

50 50 50 

(IC = 0 nM). 

50 

500 mg $207

Cyclin-Dependent Kinase (Cdk) Inhibitors, continued 




N Indirubin Derivative 

E804 

402081 A cell-permeable indirubin derivative (IDR) that blocks the Src-Stat3 signaling pathway 

and displays antitumor properties. Inhibits Cdk /E, Cdk2/A, and Cdk /B (IC 50 = 2 0 nM, 

540 nM, and .65 mM, respectively); minimally affects Jak at 0 mM. Also inhibits the 

activity of Src kinase (IC 50 = 430 nM). 

Indirubin-3´-monoxime 402085 A potent cell-permeable inhibitor of GSK-3b (IC 50 = 22 nM) and Cdks (IC 50 = 80 nM 

for Cdk and 00 nM for Cdk5). 

Indirubin-3´monoxime, 

5-Iodo- 

Indirubin-3´monoxime-5-sulphonic 

Acid 

402086 A highly potent, cell-permeable inhibitor of GSK-3b (IC = 9 nM) and Cdk 

50 

(IC = 25 nM) and Cdk5 (IC = 20 nM). Inhibition is competitive with respect to ATP. 

50 50 

402088 A potent and selective inhibitor of Cdk and Cdk5 (IC = 5 nM for Cdk ; IC = 7 nM 

50 50 

for Cdk5). Inhibition is competitive with respect to ATP. Also acts as a potent inhibitor 

of GSK-3b (IC = 80 nM). 

50 

Kenpaullone 422000 {9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one; NSC-664704} 

A potent, cell-permeable, ATP-competitive inhibitor of GSK-3b (IC 50 = 230 nM), Lck 

(IC 50 = 470 nM) and Cdks. Inhibits Cdk /cyclin B (IC 50 = 400 nM, Cdk2/cyclin A 

(IC 50 = 680 nM), Cdk2/cyclin E (IC 50 = 7.5 mM), Cdk5/p25 (IC 50 = 850 nM). Also Inhibits 

c-Src (IC 50 = 5 mM), casein kinase II (IC 50 = 20 mM), ERK (IC 50 = 20 mM), and ERK2 

(IC 50 = 9 mM) at higher concentrations. 

Olomoucine 495620 [2-(2-Hydroxyethylamino)-6-benzylamino-9-methylpurine] 

A potent, selective, ATP-competitive inhibitor of p34 cdc2 /cyclin B (IC 50 = 7 mM) and 

related kinases, including p33 cdk2 /cyclin A (IC 50 = 7 mM), p33 cdk2 /cyclin E (IC 50 = 7 mM), 

p33 cdk5 /p35 (IC 50 = 3 mM), and p44 MAPK (IC 50 = 25 mM). 

mg $88 

mg $ 0 

mg $99 

mg $99 

mg $85 

N InSolution Olomoucine 495624 A 50 mM (5 mg/336 ml) solution of Olomoucine (Cat. No. 495620) in DMSO. 5 mg $ 39 

5 mg $ 52 

Olomoucine II 495621 [6-(2-Hydroxybenzylamino)-2-((1R)-(hydroxymethyl)propyl)amino)-9-isopropylpurine] 

A cell-permeable, potent, ATP-competitive inhibitor of Cdk /cyclin B (IC = 20 nM). 

50 

Olomoucine, Iso- 495622 [6-Benzylamino-2-(2-hydroxyethylamino)-7-methylpurine; Iso-Olomoucine] 

A negative control compound for studies involving Olomoucine (Cat. No. 495620) 

(IC > 500 mM for p34 50 cdc2 /cyclin B; IC > mM for p33 50 cdk5 /p35; IC > mM for p34 50 cdk4 / 

cyclin D). 

Olomoucine, 

N9-Isopropyl- N Pfmrk Inhibitor, 

WR 2 6 74 

495623 A Cdk kinase inhibitor (IC = 2 mM) that is more potent than Olomoucine 

50 

(Cat. No. 495620). 

528140 [5-Bromo-3-(2-(4-Fluorophenyl)-2-oxoethylidine)-1,3-dihydroindol-2-one] 

A cell-permeable oxindole compound that acts as an ATP-competitive and specific inhibitor 

of Pfmrk (IC = .4 mM), a Cdk from the malaria-causing parasite Plasmodium falciparum. 

50 

Displays low activity against PfPK5 (IC = 90 mM) and human Cdk /B (IC = 29 mM). 

50 50 

Purvalanol A 540500 [2-(1R-Isopropyl-2-hydroxyethylamino)-6-(3-chloroanilino)-9-isopropyl-purine] 

A potent, cell-permeable, and selective inhibitor of Cdks (IC = 4 nM for Cdc2/cyclin B; 

50 

70 nM for Cdk2/cyclin A; 35 nM for Cdk2/cyclin E; and 75 nM for Cdk5/p35). 

Roscovitine 557360 [2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine] 

A potent, selective, ATP-competitive inhibitor of Cdks. Inhibits p34cdc2 /cyclin B 

(IC = 650 nM), p33 50 cdk2 /cyclin A (IC = 700 nM), p33 50 cdk2 /cyclin E (IC = 700 nM), 

50 

and p33cdk2 /p35 (IC = 200 nM). 

50 

mg 

5 mg 

mg 

5 mg 

$34 

$ 39 

$40 

$ 79 

5 mg $ 04 

5 mg $95 

mg $67 

N InSolution Roscovitine 557364 A 50 mM (5 mg/282 ml) solution of Roscovitine (Cat. No. 557360) in DMSO. 5 mg $ 39 

mg $46 

Roscovitine, (S)-Isomer 557362 [2-(S)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine] 

The (S)-enantiomer of Roscovitine (Cat. No. 557360). Potently inhibits p34cdc2 /cyclin B 

kinase (IC = 800 nM). 

50 

SU95 6 572650 {3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one} 

A cell-permeable, potent, and selective ATP-competitive inhibitor of Cdks (IC = 22 nM 

50 

for Cdk2/cyclin A; 40 nM for Cdk /cyclin B; and 200 nM for Cdk4/cyclin D ). 

WHI-P 80, 

Hydrochloride 

681500 [4-(3´-Hydroxyphenyl)amino-6,7-dimethoxyquinazoline, HCl] 

An ATP-competitive inhibitor of Cdk2 (IC 50 = mM). 

Cyclin-Dependent Protein Kinase Inhibitor Set 

Contains 5 mg of Olomoucine (Cat. No. 495620), mg of Iso-Olomoucine (Cat. No. 495622), and mg of Roscovitine (Cat. No. 557360). 

Cat. No. 219428 1 set $163 

mg 

5 mg 

$35 

$ 39 

5 mg $ 00 

500 mg 

mg 

$79 

$ 27 


Phone 800 628 8470 


7


DNA-Dependent Protein Kinase (DNA-PK) Inhibitors 

DNA-dependent protein kinase (DNA-PK) is a trimeric 

nuclear serine/threonine kinase composed of a large 

catalytic subunit and two DNA-targeting proteins, Ku70 

and Ku80. The catalytic subunit, by itself, is inactive. It 

relies on other DNA-PK components to direct it to the 

DNA and trigger its kinase activity. The amino acid 

sequence of the DNA-PK suggests that it is a member of the 

phosphatidylinositol-3-kinase (PI 3-K) superfamily. DNA- 

PK recognizes and initiates repair of DNA double-strand 

breaks produced by ionizing radiation and certain drugs. 

DNA-PK phosphorylates protein targets and 

also undergoes auto-phosphorylation. The autophosphorylation 

activity has been shown to be 

essential for repair of random double-strand breaks. 

DNA-PK phosphorylates p53 on Ser 15 and Ser 37 leading 

to stabilization and inhibition of p53 degradation by 

MDM2. Phosphorylation of Ser 15 is suggested to be 

essential for p53 function. Ser 15 resides within the 

critical N-terminal region of p53, which controls the 

interaction of p53 with the transcriptional apparatus 

and with the MDM2 protein. Phosphorylation of Ser 15 

weakens both the association of p53 with MDM2 and the 

DNA-Dependent Protein Kinase (DNA-PK) Inhibitors 

repression of p53 by MDM2. Phosphorylation of DNA-PK 

by the PKC d catalytic fragment leads to the dissociation 

of DNA-PK from DNA, resulting in its inactivation. 

DNA-PK represents a new target for cancer drug 

development. Cells defective in DNA-PK components 

are reported to be hypersensitive to killing by ionizing 

radiation owing to their inability to repair doublestranded 

breaks effectively. A number of small molecule 

inhibitors of DNA-PK catalytic subunit have been 

developed, which sensitize cells to DNA-damaging 

agents, but are relatively nontoxic in the absence of DNA 

breaks. These inhibitors may have clinical potential in 

the treatment of cancer. 

References: 

Collis, S.J., et al. 2005. Oncogene 24, 949. 

Wechsler, T., et al. 2004. Proc. Natl. Acad. Sci. USA 101, 247. 

Basu, A., 2003. J. Cell. Mol. Med. 7, 34 . 

Kashishian, A., et al. 2003. Mol. Cancer Ther. 2, 257. 

Woo, R.A., et al. 998. Nature 394, 700. 

Jackson, S.P., and Jeggo, P.A. 995. Trends Biochem. Sci. 20, 4 2. 

More online... www.calbiochem.com/inhibitors/DNAPK 


DNA-PK Inhibitor 260960 (4,5-Dimethoxy-2-nitrobenzaldehyde; DMNB; DNA-Dependent Protein Kinase Inhibitor) 

A cell-permeable vanillin derivative that acts as a potent and selective inhibitor of 

DNA-PK (IC 50 = 5 mM) and DNA-PK-mediated double-strand break. 

DNA-PK Inhibitor II 260961 {DNA-Dependent Protein Kinase Inhibitor II; 2-(Morpholin-4-yl)-benzo[h]chromen-4-one; 

NU7026} 

A cell-permeable, potent, specific, and ATP-competitive inhibitor of DNA-PK (IC 50 = 230 nM). 

It is highly selective towards DNA-PK over other PI 3-kinase related enzymes (IC 50 = 3 mM 

for PI 3-kinase and > 00 mM for ATM and ATR). 

N DNA-PK Inhibitor III 260962 [1-(2-Hydroxy-4-morpholin-4-yl-phenyl)ethanone; IC86621] 

A cell-permeable aryl-morpholino compound that acts as a potent, selective, ATPcompetitive 

inhibitor of DNA-PK (IC 50 = 20 nM) and PI 3-kinase catalytic subunit p 0b 

(IC 50 = 35 nM). It inhibits DNA-PK-mediated cellular DNA DSB (double-strand break) 

repair (EC 50 = 68 mM) and enhances DSB-induced antitumor activity both in vitro and in 

vivo. 

N DNA-PK Inhibitor IV 260963 (2-Hydroxy-4-morpholin-4-yl-benzaldehyde; IC60211) 

A morpholino-salicylaldehyde compound that acts as a potent, selective and ATPcompetitive 

inhibitor of DNA-PK (IC 50 = 430 nM). Inhibits PI 3-kinase catalytic subunit 

p 0-isozymes at higher concentrations (IC 50 = 0 mM, 2.8 mM, 5. mM, and 37 mM 

for a, b, d and g, respectively) and weakly inhibits a panel of several other kinases, 

including, ATM, CKII, GRK2, mTOR, PI3KC2a, PI3KC2b, PI3KC2g, and PI4Kb, even at 

50 mM. 

N DNA-PK Inhibitor V 260964 [AMA37; ArylMorpholine Analog 37; 1-(2-Hydroxy-4-morpholin-4-yl-phenyl)- 

phenyl-methanone] 

A potent, selective, and ATP-competitive inhibitor of DNA-PK (IC 50 = 270 nM). Inhibits 

PI 3-kinase catalytic subunit p 0-isozymes at higher concentrations (IC 50 = 32 mM, 

3.7 mM, 22 mM, and ~ 00 mM for a, b, d,and g, respectively) and weakly inhibits a panel 

of several other kinases, including, ATM, ATR, CKII, GRK2, mTOR, PI3KC2a, PI3KC2b, 

PI3KC2g, and PI4Kb, even at 50 mM. 

0 mg $68 

5 mg $ 37 

mg $84 

8 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

mg 

5 mg 

$73 

$237 

$90 

$288

Glycogen Synthase Kinase-3 (GSK-3) Inhibitors 

Glycogen synthase kinase-3 (GSK-3), a multifunctional 

serine/threonine kinase, is a key regulator of numerous 

signaling pathways. Two isoforms of GSK-3 are reported 

in mammals: a 51 kDa GSK-3a and a 47 kDa GSK-3b. 

GSK-3b is constitutively active in resting cells and 

treatment of cells with an agent, such as insulin, is 

shown to cause GSK-3 inactivation through a PI 3kinase 

(PI 3-K)-dependent mechanism. PI 3-K-induced 

activation of PKB/Akt results in phosphorylation of 

Ser 21 on GSK-3a and Ser 9 on GSK-3b, which inhibits 

GSK-3 activity. The phosphorylated N-terminus becomes 

a primed pseudosubstrate that occupies the positive 

binding pocket and the active site of the enzyme and 

acts as a competitive inhibitor for true substrates. This 

prevents phosphorylation of substrates. Arg 96 is shown 

to be a crucial component of the positive pocket that 

binds primed substrates. Small molecule inhibitors that 

fit in the positively charged pocket of the kinase domain 

of GSK-3b are useful for selectively inhibiting primed 

substrates. Several known GSK-3 substrates participate in 

a wide spectrum of cellular processes, including glycogen 

Glycogen Synthase Kinase Inhibitors 



metabolism, transcription, translation, cytoskeletal 

regulation, intracellular vesicular transport, cell cycle 

progression, and apoptosis. Phosphorylation of these 

substrates by GSK-3b usually has an inhibitory effect. 

Abnormalities in pathways that use GSK-3 as a regulator 

have been linked to several disease conditions. Hence, 

GSK-3 has emerged as a potential therapeutic target, 

particularly in non-insulin-dependent diabetes mellitus, 

Alzheimer’s disease, developmental disorders, and 

cancer. Several new GSK-3 inhibitors have recently been 

developed, most of which act in an ATP competitive 

manner. Inhibitors belonging to aloisines, the paullones, 

and the maleimide families, have shown promise as 

therapeutic agents. Due to its involvement in multiple 

pathways, selectivity of GSK-3 inhibition is an important 

factor in the development of inhibitors for therapeutic 

applications. 


Aloisine A 128125 {7-n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP107} 

An inhibitor of GSK-3 (IC 50 = 500 nM for GSK-3a and .5 mM for GSK-3b). Also acts as a 

potent, selective, reversible, and ATP-competitive inhibitor of Cdks (IC 50 = 50 nM for Cdk / 

cyclin B, 20 nM for Cdk2/cyclin A, 400 nM for Cdk2/cyclin E, and 60 nM for Cdk5/p35). 

Aloisine, RP 06 128135 {7-n-Butyl-6-(4-methoxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP106} 

A cell-permeable, potent, selective ATP-competitive inhibitor of Cdk /cyclin B 

(IC 50 = 700 nM), Cdk5/p25 (IC 50 = .5 mM), and GSK-3 (IC 50 = 920 nM). 

Alsterpaullone 126870 {9-Nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one} 

A potent inhibitor of Cdk /cyclin B (IC 50 = 35 nM). Also inhibits the activity of Cdk5/p25dependent 

phosphorylation of DARPP-32. One of the most active paullones that acts by 

competing with ATP for binding to GSK-3b and inhibits the phosphorylation of tau. 

N Alsterpaullone, 2- 

Cyanoethyl 

More online... www.calbiochem.com/inhibitors/GSK 

126871 An Alsterpaullone (Cat. No. 26870) derivative that acts as a highly potent, ATPcompetitive, 

and selective inhibitor of Cdk /B and GSK-3b (IC 50 = 230 pM and 800 pM, 

respectively; [ATP] = 5 mM). Displays ~37-fold greater selectivity over Cdk5/p25 (IC 50 = 

30 nM). Shown to inhibit other kinases in a commercially available testing screen panel 

(pIC 50 = -logIC 50 [M]; pIC 50 ~7.5, 7.0, 7.0, 6.5, 6.5, 6.0, and 6.0 for Cdk2/A, Cdk4/D , 

GSK-3b, PDGFRb, Src, VEGFR-2, and VEGFR-3, respectively; [ATP] = mM). 

N -Azakenpaullone 191500 A Kenpaullone (Cat. No. 422000) analog that acts as a potent and ATP-competitive 

inhibitor of GSK-3b (IC 50 = 8 nM), and displays ~ 00-200 fold greater selectivity 

over Cdk /B and Cdk5/p25 (IC 50 = 2.0 mM and 4.2 mM, respectively). 

N Cdk /2 Inhibitor III 217714 A cell-permeable triazolo-diamine compound that acts as a highly potent ATPcompetitive 

inhibitor of Cdk /B and Cdk2/A (IC 50 = 600 pM and 500 pM) with selectivity 

over VEGF-R2 and GSK-3b (IC 50 = 32 nM and 40 nM). Only minimally affects a panel of 

kinases tested (IC 50 = .0 mM, .6 mM, 2.8 mM, 5.2 mM, 8.9 mM, > 0 mM and 

> 00 mM for ERK-2, PDGF-Rb, CKI, PKA, CaMKII, EGF-R or insulin kinase-b, and CKII, 


5 mg $90 

5 mg $73 

mg $83 

mg $ 39 

mg $98 

mg $88 


Phone 800 628 8470 


9


Glycogen Synthase Kinase Inhibitors, continued 


Cdk /5 Inhibitor 217720 (3-Amino-1H-pyrazolo[3,4-b]quinoxaline) 

A pyrazoloquinoxaline compound that effectively inhibits Cdk /B, Cdk 5/p25, and 

GSK-3b (IC 50 = 0.6 mM, 0.4 mM, and mM respectively). 

GSK-3b Inhibitor I 361540 (TDZD-8; 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) 

A thiadiazolidinone (TDZD) analog that acts as a highly selective, non-ATP competitive 

inhibitor of GSK-3b (IC 50 = 2 mM). Proposed to bind to the active site of GSK-3b. 

GSK-3b Inhibitor II 361541 {Glycogen Synthase Kinase-3b Inhibitor II; 2-Thio(3-iodobenzyl)-5-(1-pyridyl)- 

[1,3,4]-oxadiazole} 

A 2-thio-[ ,3,4]-oxadiazole-pyridyl derivative that acts as a potent inhibitor of GSK-3b 

(IC 50 = 390 nM). 

GSK-3b Inhibitor III 361542 (2,4-Dibenzyl-5-oxothiadiazolidine-3-thione; OTDZT) 

An oxothiadiazolidine-3-thione analog that acts as a non-ATP competitive inhibitor of 

GSK-3b (IC 50 = 0 mM). 

N GSK-3b Inhibitor VI 361547 [2-Chloro-1-(4,5-dibromo-thiophen-2-yl)-ethanone] 

A thienyl a-chloromethyl ketone compound that acts as a cell-permeable, irreversible, 

and non-ATP competitive inhibitor of GSK-3b (IC 50 = mM). This reactive alkylating 

agent is selective towards GSK-3b and does not affect PKA activity even at 

concentrations as high as 00 mM. 

GSK-3b Inhibitor VII 361548 (a-4-Dibromoacetophenone; Tau Protein Kinase I Inhibitor; TPK I Inhibitor) 

A cell-permeable, selective, irreversible, and non-ATP competitive inhibitor of GSK-3b 

(IC 50 = 500 nM). 

GSK-3b Inhibitor VIII 361549 [AR-A014418; N-(4-Methoxybenzyl)-N´-(5-nitro-1,3-thiazol-2-yl)urea] 

A cell-permeable, potent, and highly specific inhibitor of glycogen synthase kinase-3b 

(GSK-3b) (IC 50 = 04 nM). Inhibition is competitive with respect to ATP (K i = 38 nM). 

N InSolution GSK-3b 

Inhibitor VIII 

5 mg $ 8 

5 mg $83 

5 mg $89 

mg $62 

5 mg $95 

5 mg $84 

5 mg $84 

361557 A 25 mM (5 mg/649 ml) solution of GSK-3b Inhibitor VIII (Cat. No. 36 549) in DMSO. 5 mg $84 

GSK-3 Inhibitor IX 361550 [BIO; (2´Z,3É)-6-Bromoindirubin-3´-oxime] 

A cell-permeable, highly potent, selective, reversible, and ATP-competitive 

inhibitor of GSK-3a/b (IC 50 = 5 nM). At higher concentrations, inhibits Cdk2/cyclin A 

(IC 50 = 300 nM) and Cdk5/p25 (IC 50 = 83 nM). 

N InSolution GSK-3 

Inhibitor IX 

mg $95 

361552 A 0 mM (500 mg/ 40 ml) solution of GSK-3 Inhibitor IX (Cat. No. 36 550) in DMSO. 500 mg $63 

N GSK-3 Inhibitor X 361551 [BIO-Acetoxime; (2´Z,3É)-6-Bromoindirubin-3´-acetoxime] 

An acetoxime analog of BIO (GSK-3 Inhibitor IX, Cat. No. 36 550) that exhibits greater 

selectivity for GSK-3a/b (IC 50 = 0 nM) over Cdk5/p25, Cdk2/A, and Cdk /B 

(IC 50 = 2.4 mM, 4.3 mM, and 63 mM, respectively). 

N GSK-3b Inhibitor XI 361553 {3-(1-(3-Hydroxypropyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-4-pyrazin-2-yl-pyrrole-2, 

5-dione} 

N GSK-3b Inhibitor XII, 

TWS 9 

A cell-permeable azaindolylmaleimide compound that acts as a potent, specific, and 

ATP-competitive inhibitor of GSK-3b (K i = 25 nM) and minimally inhibits a panel of 79 

commonly studied protein kinases, including several PKC isozymes. Shown to increase 

intracellular glycogen synthase activity in HEK293 cells with an EC 50 of 32 nM and 

demonstrate metabolic stability in human liver microsomes (HLM; t /2 > 00 min). 

361554 (Neurogenesis Inducer, TWS119) 

A cell-permeable pyrrolopyrimidine compound that acts as a potent and selective 

inhibitor of GSK-3b (IC 50 = 30 nM). Binds to GSK-3b with high-affinity (K d = 26 nM) 

and increases the level of b-catenin, a downstream substrate of GSK-3b in the Wnt 

signaling pathway. 

N GSK-3 Inhibitor XIII 361555 [(5-Methyl-1H-pyrazol-3-yl)-(2-phenylquinazolin-4-yl)amine] 

An aminopyrazole compound that acts as a potent and ATP-binding site inhibitor 

of GSK-3 with a K i of 24 nM. 

N GSK-3 Inhibitor XIV, 

Control, MeBIO 

361556 (1-Methyl-BIO) 

A cell-permeable N-methylated analog of GSK-3 Inhibitor IX, BIO (Cat. No. 36 550) 

that serves as a relevant kinase inactive control (IC 50 > 92 mM for Cdk /B, and > 00 mM 

for Cdk5/p25 and GSK-3a/b). 

mg $95 

mg $ 32 

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mg 

5 mg 

mg 

5 mg 

$90 

$278 

$67 

$20 

mg $93

Glycogen Synthase Kinase Inhibitors, continued 




GSK-3b Peptide 

Inhibitor 

GSK-3b Peptide 

Inhibitor, Cellpermeable 


damicornis 

361545 (H-KEAPPAPPQSpP-NH 2 ; L803) 

A phosphorylated peptide that acts as a substrate-specific, competitive inhibitor of 

GSK-3b (IC 50 = 50 mM). Inhibits Cdc2, CK II, MAPK, PKA, PKB, and PKC d at higher 

concentrations (200 mM results in 85– 00% inhibition). 

361546 (L803-mts; Myr-N-GKEAPPAPPQSZP-NH 2 ) 

A cell-permeable, myristoylated form of GSK-3b Peptide Inhibitor (Cat. No. 36 545) 

with a glycine spacer. Acts as a selective, substrate-specific, competitive inhibitor of 

GSK-3b (IC 50 = 40 mM). Does not affect the activities of Cdc2, PKB, or PKC. 


[2,3-c]azepin-8-one; HD; 10Z-Hymenialdisine} 

A potent, ATP-competitive inhibitor of GSK-3b (IC 50 = 0 nM). Also inhibits several other 

protein kinases, including MEK- (IC 50 = 6 nM), Cdks (IC 50 = 22 nM for Cdk /cyclin B, 

40 nM for Cdk2/cyclin E, and 28 nM for Cdk5/p35), and casein kinase (IC 50 = 35 nM). 

Indirubin-3´-monoxime 402085 A potent cell-permeable inhibitor of GSK-3b (IC 50 = 90 nM) and cyclin-dependent 

kinases (IC 50 = 80 nM for Cdk ). 

Indirubin-3´-monoxime, 

5-Iodo- 

Indirubin-3´monoxime-5-sulphonic 

Acid 

402086 A highly potent, cell-permeable inhibitor of GSK-3b (IC 50 = 9 nM). Reported to inhibit 

GSK-3b phosphorylation of human tau protein in vitro (IC 50 ~ 00 nM) and in cells (effective 

concentration = 20 mM). Also inhibits Cdk (IC 50 = 25 nM) and Cdk5 (IC 50 = 20 nM). 

402088 A highly potent, selective, and ATP competitive inhibitor of Cdks and 5 (IC 50 = 5 nM for 

Cdk ; IC 50 = 7 nM for Cdk5). Also acts as a potent inhibitor of GSK-3b (IC 50 = 80 nM). 

ICG 371957 A cell-permeable alkaloid-containing indole/maleimide/imidazole skeleton that acts 

as a potent and ATP-competitive inhibitor of Chk (IC 50 = 00 nM) and GSK-3b (IC 50 = 

500 nM). Inhibits G 2 DNA damage checkpoint-associated kinases, Chk2, Cdk , and DNA- 

PK only at much higher concentrations (IC 50 = 3 µM, 0 µM, and 0 µM, respectively). 

Kenpaullone 422000 {9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one; NSC-664704} 

A potent, cell-permeable, ATP-competitive inhibitor of GSK-3b (IC 50 = 230 nM), 

Lck (IC 50 = 470 nM) and Cdks. Inhibits Cdk /cyclin B (IC 50 = 400 nM), CdK2/cyclin A 

(IC 50 = 680 nM), Cdk2/cyclin E (IC 50 = 7.5 mM), and Cdk5/p25 (IC 50 = 850 nM). 

Ro-3 -8220 557520 {3-[1-[3-(Amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide; 

Bisindolylmaleimide IX, Methanesulfonate} 

A potent, cell-permeable inhibitor of GSK-3. Inhibits GSK-3 in primary adipocytes 

(IC 50 = 6.8 nM and in GSK-3b immunoprecipitates (IC 50 = 2.8 nM). Also acts as a 

competitive and selective inhibitor of CaM kinase II (IC 50 = 7 mM) and protein kinase A 

(IC 50 = 900 nM). 

mg $90 

mg $ 24 

500 mg $207 

mg $ 0 

mg $99 

mg $99 

mg $ 39 

mg $85 

500 mg $83 

To view all GSK research-related 

products and to request your free 

GSK-3b and b-catenin signaling 

wall poster, visit our GSK 

Interactive Pathways at 

www.calbiochem.com/gsk 


Phone 800 628 8470 


2


c-Jun N-Terminal Kinase (JNK/SAP Kinase) Inhibitors 

Jun N-terminal kinase (JNK), a serine-directed protein 

kinase, is involved in the phosphorylation and activation 

of c-Jun and ATF2 and plays a significant role in 

metabolism, growth, cell differentiation, apoptosis, and 

participates in stress responses, such as those induced 

by hypoxin, cold shock, and hyperosmolarity. The 

three isoforms of JNK, known as JNK1, 2, and 3, are 

encoded by 3, independent genes. They phosphorylate 

Ser 63 and Ser 73 at the region of c-Jun and enhance its 

c-Jun N-Terminal Kinase (JNK/SAP Kinase) Inhibitors 

transcriptional activity. JNK1 and 2 exhibit broad tissue 

expression profiles. In contrast, JNK3 is expressed 

predominantly in the central nervous system. JNK is 

activated in response to inflammation, endotoxins, and 

environmental stress. Its activation can mediate proinflammatory 

gene expression, cell proliferation and 

apoptosis. 


Dicoumarol 287897 [Bishydroxycoumarin; Dicumarol; 3,3´-Methylenebis(4-hydroxycoumarin)] 

A quinone reductase inhibitor that competes with NADH or NADPH for binding to the 

oxidized form of NAD(P)H:quinone oxidoreductase (NQO ). Shown to inhibit IGF-I-, 

menadione-, and DMNQ-mediated activation of stress-activated protein kinase/SAPK/ 

JNK and subsequent phosphorylation of c-Jun, as well as stress-induced activation of 

SAPK/JNK. Does not affect the phosphorylation of p38 or Akt (protein kinase B). 

JNK Inhibitor I, (L)- 

Form, Cell-Permeable 

JNK Inhibitor I, (L)- 

Form, Cell-Permeable, 

Negative Control 

420116 [(L)-HIV-TAT 48-57 -PP-JBD 20 ; (L)-JNKI1; c-Jun NH 2 -terminal kinase; H- 

GRKKRRQRRRPPRPKRPTTLNLFPQVPRSQDT-NH 2 ; SAPK Inhibitor I] 

A cell-permeable, biologically active peptide consisting of a carboxyl-terminal sequence 

derived from the JNK-binding domain (JBD) and an amino-terminal peptide containing 

the HIV-TAT 48-57 sequence that imparts cell-permeability. Blocks the activation domain 

of JNK and prevents the activation of c-Jun (IC 50 ~ mM). Inhibits IL- b-induced c-Jun 

and c-fos expression in insulin secreting bTC-3 cells and offers protection against 

apoptosis. Does not affect the activities of ERK , ERK2, or p38 in any significant manner. 

420118 [(L)-HIV-TAT 48-57 -PP; GRKKRRQRRRPP-NH 2 ] 

A highly cell-permeable carrier decapeptide derived from HIV-TAT 48-57 sequence that 

is modified with two proline residues. Serves as a useful negative control for studies 

involving JNK Inhibitor I, (L)-Form, Cell-Permeable (Cat. No. 420 6). 

JNK Inhibitor II 420119 {Anthra[1,9-cd]pyrazol-6(2H)-one; 1,9-pyrazoloanthrone; SAPK Inhibitor II; SP600125} 

A potent, cell-permeable, selective, and reversible inhibitor of JNK (IC 50 = 40 nM for 

JNK- and JNK-2 and 90 nM for JNK-3). The inhibition is competitive with respect to 

ATP. Exhibits over 300-fold greater selectivity for JNK as compared to ERK and p38b 

MAP kinases. 

N InSolution JNK 

Inhibitor II 

JNK Inhibitor II, 


JNK Inhibitor III, 

Cell-Permeable 

More online... www.calbiochem.com/inhibitors/JNK 

500 mg $50 

mg $2 4 

mg $ 06 

5 mg $64 

420128 A 50 mM (5 mg/454 ml) solution of JNK Inhibitor II (Cat. No. 420 9) in DMSO. 5 mg $64 

420123 (N 1 -Methyl-1,9-pyrazoloanthrone) 

A useful negative control for JNK Inhibitor II (SP600 25, Cat. No. 420 9). Inhibits JNK2 

and JNK3 only at much higher concentrations (IC 50 = 8 mM and 24 mM, respectively) 

compared to JNK Inhibitor II (IC 50 = 40 and 90 nM, respectively). 

420130 (Ac-YGRKKRRQRRR-gaba-ILKQSMTLNLADPVGSLKPHLRAKN-NH 2 ; HIV-TAT 47-57 -gaba-c- 

Jund 33-57 ; SAPK Inhibitor III) 

A cell-permeable peptide constructed by fusing the JNK binding domain sequence (d) 

(amino acids 33–57) of human c-Jun to the HIV-TAT transduction domain sequence 

(amino acids 47–57) with a g-aminobutyric acid (GABA) spacer. Disrupts c-Jun/JNK 

complex formation and subsequent phosphorylation and activation of c-Jun by JNK 

in vitro and in intact cells. Mode of inhibition is distinct from that of JNK Inhibitor II 

(SP600 25; Cat. No. 420 9). 

mg $57 

mg $ 73 

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c-Jun N-Terminal Kinase (JNK/SAP Kinase) Inhibitors, continued 


Call us or visit 

our website 



JNK Inhibitor III, 

Cell-Permeable, 


420131 (Ac-YGRKKRRQRRR-gaba-DSNLIRGVLPTLMPKSLAQNKLKHA-NH 2 ; HIV-TAT 47-57 -gaba-c- 

Jund 33-57 , scrambled) 

A cell-permeable peptide that contains a scrambled sequence derived from the JNK 

binding domain (d) of human c-Jun (amino acids 33–57) fused to the HIV-TAT transduction 

domain (amino acids 47–57) via a g-aminobutyric acid (GABA) spacer. Does not 

disrupt c-Jun/JNK complex formation. Serves as a negative control for JNK Inhibitor III, 

Cell-Permeable (Cat. No. 420 30). 

N JNK Inhibitor V 420129 A cell-permeable pyrimidinyl compound that acts as a potent, selective, and ATPcompetitive 

inhibitor of c-Jun N-terminal kinase (IC 50 = 50, 220, and 70 nM for 

hJNK , hJNK2, and hJNK3, respectively; 20 nM for rat JNK3) with 0– 00-fold greater 

selectivity over a panel of commonly studied kinases (IC 50 in the range of –5 mM for 

c-Src, c-Raf, Cdk2/A, and p38a; 5– 0 mM for MKK6, RSK-2, ROCKII, Blk, MSK , and SGK; 

> 0 mM for Erk , MEK , PDK , Akt, IKKb, and Chk ). 

NPPB 484100 5-Nitro-2-(3-phenylpropylamino)benzoic Acid 

Blocks phosphorylation and activation of ERK /2 and JNK/SAPK, but not p38. 

Protein Kinase Inhibitor, 

DMAP 

IP3 Kinase Inhibitor 

476493 (N 6 ,N 6 -Dimethyladenine; 6-Dimethylaminopurine; 6 DMAP) 

A puromycin analog that acts as a protein kinase inhibitor. Reported to inhibit a number 

of TNF-a-induced effects, including CAP kinase activation, JNK activity, and suppression 

of Jun-B expression. DMAP treatment of Xenopus eggs initiates rapid DNA 

synthesis. 

mg $ 73 

5 mg $ 44 

0 mg $62 

50 mg $48 


IP3K Inhibitor 406170 A cell-permeable, selective, ATP-competitive inhibitor of IP 3-K (IC 50 = 0.2 µM), 

the kinase that catalyzes the conversion of IP3 (Cat. Nos. 407 23 and 407 37) 

to IP4 (Cat. No. 407 26). Induces elevated cellular IP3 level and Ca 2+ -release in a 

dose-dependent manner (5–20 mM in HL60 cells). 

5 mg $ 8 

www.calbiochem.com/phosphodetect 


Phone 800 628 8470 


23


Mitogen-Activated Protein (MAP) Kinase Inhibitors 

The mitogen-activated protein (MAP) kinases are a group 

of evolutionarily conserved protein serine/threonine 

kinases that are activated in response to a variety of 

extracellular stimuli and mediate signal transduction 

from the cell surface to the nucleus. They regulate several 

physiological and pathological cellular phenomena, 

including inflammation, apoptotic cell death, oncogenic 

transformation, tumor cell invasion, and metastasis. MAP 

kinases, in combination with several other signaling 

pathways, can differentially alter the phosphorylation 

status of transcription factors in a pattern unique to 

a given external signal. Although MAP kinases are 

expressed in all cell types, they regulate very specific 

biological responses that differ from cell type to cell type. 

Four major types of MAP kinase cascades have been 

reported in mammalian cells that respond synergistically 

to different upstream signals. MAP kinases are part 

of a three-tiered phospho-relay cascade consisting of 

MAP kinase, a MAP kinase kinase (MEK) and a MAP 

kinase kinase kinase (MEKK). Controlled regulation 

of these cascades is involved in cell proliferation and 

differentiation, whereas unregulated activation of 

these MAP kinases can result in oncogenesis. The most 

widely studied cascade is that of ERK1/ERK2 MAP 

kinases. In the cell, one highly active form of ERK1 or 

ERK2 (dual phosphorylated) exists, which exhibits over 

1000-fold greater activity than the unphosphorylated 

form. At any one time, there may be three low activity 

forms of ERKs: one unphosphorylated enzyme, and two 

singly phosphorylated forms that contain 

phosphate either at a tyrosine or a 

threonine residue. 

The JNK/SAPK cascade is 

activated following exposure 

to UV radiation, 

heat shock, or 

inflammatory 

cytokines. The 

activation of these 

MAP kinases is 

mediated by Rac 

and cdc42, two 

small G-proteins. 

Activated cdc42 

binds to PAK protein 

kinase and activates 

it. Activated PAK 65 can 

activate MEKK, which in turn phosphorylates SEK/JNKK 

and activates it. The active SEK/JNKK phosphorylates 

JNK/SAPK (at the TPY motif). The sites of activating 

phosphorylation are conserved between ERK and JNK, 

however, these sites are located within distinct dual 

specificity phosphorylation motifs (TPY for JNK and 

TEY for ERK). 

The p38 kinase, another member of the MAP kinase 

family, bears similarity to the yeast MAPK, Hog-1. It 

is activated in response to inflammatory cytokines, 

endotoxins, and osmotic stress. It shares about 50% 

homology with the ERKs. The upstream steps in its 

activation of this cascade are not well defined. However, 

downstream activation of p38 occurs following its 

phosphorylation (at the TGY motif) by MKK3, a dual 

specificity kinase. Following its activation, p38 

translocates to the nucleus and phosphoryates ATF-2. 

Another known target of p38 is MAPKAPK2 that is 

involved in the phosphorylation and activation of heatshock 

proteins. 

The fourth and least studied mammalian MAP kinase 

pathway is big MAP kinase 1 (BMK1), also known as 

extracellular signal regulated kinase 5 (ERK5). BMK1 

is activated in response to growth factors and stress. 

Activation of the BMK1 signaling pathway has not 

only been implicated in normal cell survival, cell 

proliferation, cell differentiation, but also in 

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Mitogen-Activated Protein (MAP) Kinase Inhibitors, continued 

pathological states such as carcinogenesis, cardiac 

hypertrophy, and atherosclerosis. BMK1 can be activated 

following exposure EGF, BDNF, NGF, VEGF, FGF-2, 

phorbol esters, and oxidative stress. The signaling 

molecules in the ERK5 cascade include MEKK2/3, MEK5, 

and ERK5. Since BMK1 is the only known substrate of 

MEK5, all effects of MEK5 have been attributed to its 

ability to activate BMK1. Thus far, myocyte enhancer 

factor 2 (MEF-2), Ets-domain transcription factor (Sap1a), 

Bad, and serum- and glucocorticoid-inducible kinase 

(SGK) have been identified as substrates for BMK1. 

Although different MAP kinase cascades show a high 

degree of specificity and functional separation, some 

degree of cross-talk is observed between different 

pathways. Another important observation is that when 

mammalian cells are treated with mitogenic agents, 

ERKs are significantly activated whereas JNK/SAPK are 

not affected. Conversely, cells exposed to stress activate 

the JNK/SAPK pathway without altering the activity of 

MAP Kinase Inhibitors 



ERKs. At the transcription level, even though ATF-2 is 

phosphorylated and activated by all three MAP kinases, 

and c-Jun and Elk-1 are phosphorylated by ERKs and 

JNK/SAPK, all these pathways result in transcriptional 

activity that is unique for a particular external stress. 

References: 

Wong, C. H., et al. 2005. Dev. Biol. 286, . 

Johnson, G.L. et al. 2005. Curr. Opin. Chem. Biol. 9, 325. 

Hayashi, M., and Lee, J.D. 2004. J. Mol. Med. 82, 800. 

Murry, J. A., 2003. Curr. Opin. Drug. Discov. Develop. 6, 945. 

Burack, W.R., and Sturgill, T.W. 997. Biochemistry 36, 5929. 

Sivaraman, V.S., et al. 997. J. Clin. Invest. 99, 478. 

Tong, L., et al. 997. Nat. Struct. Biol. 4, 3 . 

Su, B., and Karin, M. 996. Curr. Opin. Immunol. 8, 402. 

Cheng, M., et al. 996. J. Biol. Chem. 271, 895 . 

Das, R., and Vonderhaar, B.K. 996. Breast Cancer Res. Treat. 40, 4 . 

Davis, R.J., 994. Trends Biochem. Sci. 19, 470. 


AG 26 658452 [a-Cyano-(3-hydroxy-4-nitro)cinnamonitrile] 

An inhibitor of lipopolysaccaride (LPS)-induced synthesis of tumor necrosis factor-a 

and nitric oxide in murine peritoneal macrophages. Blocks LPS-induced tyrosine 

phosphorylation of a p42 MAPK /ERK2 protein substrate. 

Anthrax Lethal Factor, 

Recombinant, Bacillus 

anthracis 

ERK Activation Inhibitor 

Peptide I, Cell- 

Permeable 

ERK Activation Inhibitor 

Peptide II, Cell- 

Permeable 

More online... www.calbiochem.com/inhibitors/MAPK 

176900 One of the three protein components of Anthrax toxin, lethal factor (LF) is a highly 

specific protease that cleaves members of the mitogen-activated protein kinase kinase 

(MAPKK) family. LF is comprised of four domains. Domain I binds the protective antigen 

to enter the target cell; domains II, III, and IV create a long groove to hold and cleave the 

MAPKK proteins. 

328000 (Ste-MEK1 13 ; Ste-MPKKKPTPIQLNP-NH 2 ) 

A stearated 3-amino acid peptide corresponding to the N-terminus of MEK . Acts as a 

specific inhibitor of ERK activation and the transcriptional activity of Elk . Selectively binds 

to ERK2 and prevents its interaction with MEK (IC 50 = 2.5 mM). 

328005 (H-GYGRKKRRQRRR-G-MPKKKPTPIQLNP-NH 2 ; MTP TAT -G-MEK1 13 ) 

A 3-amino acid peptide corresponding to the N-terminus of MEK that is fused to the 

HIV-TAT membrane translocating peptide (MTP) sequence via a glycine linker. Acts as a 

specific inhibitor of ERK activation and the transcriptional activity of Elk by binding to 

ERK2, and prevents its interaction with MEK (IC 50 = 2 0 nM). 

N ERK Inhibitor 328006 A cell-permeable thiazolidinedione compound with anti-proliferative properties 

(IC 50 ≤ 25 mM in HeLa, A549, and SUM- 59 tumor cells). Preferentially binds to ERK2 with 

a K d of ~5 mM and prevents its interaction with protein substrates. Shown to block ERKmediated 

phosphorylation of ribosomal S6 kinase- (Rsk- ) and ternary complex factor Elk- , 

with little effect on ERK /2 phosphorylation by its upstream activator MEK /2. 

Hsp25 Kinase Inhibitor 385880 (KKKALNRQLGVAA; MAPKAP Kinase-2 Inhibitor; MK2 Inhibitor) 

A potent and selective inhibitor of mammalian heat-shock protein (Hsp25) kinase (mitogenactivated 

protein kinase-activated protein kinase-2 (MAPKAP kinase-2). Inhibition is 

competitive with respect to the substrate peptide (K i = 8. mM) and non-competitive 

with respect to ATP (K i = 34 mM). 

5 mg $97 

00 mg $232 

mg $ 30 

mg $ 73 

5 mg $88 

mg $90 


Phone 800 628 8470 


25


MAP Kinase Inhibitors, continued 



damicornis 


[2,3-c]azepin-8-one; HD; 10Z-Hymenialdisine} 

A potent, ATP-competitive inhibitor of GSK-3b (IC 50 = 0 nM). Also inhibits several other 

protein kinases, including MEK- (IC 50 = 6 nM), Cdks (IC 50 = 22 nM for Cdk /cyclin B, 

40 nM for Cdk2/cyclin E, and 28 nM for Cdk5/p35), and casein kinase (IC 50 = 35 nM). 

5-Iodotubercidin 407900 {4-Amino-5-iodo-7-(b-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine; ITU} 

A potent inhibitor of adenosine kinase (K i = 30 nM) and Ser/Thr-specific kinases that also 

acts as a potent, and competitive inhibitor of ERK2 (K i = 530 nM). 

N MEK Inhibitor I 444937 A cell-permeable pyridine-containing vinylogous cyanamide compound that acts 

as a potent and selective inhibitor of MEK (IC 50 = 2 nM) with little activity towards 

MKK3 and MKK4 (IC 50 > mM). The inhibition is noncompetitive with respect to ERK 

and the compound displays significant affinity only towards ATP-bound MEK 

(i.e., noncompetitive with respect to ATP). Exhibits superior potency, solubility, and 

stability compared to U0 26 (Cat. No. 662005) in aqueous solutions. 

MEK /2 Inhibitor 444939 [Z-& E-a-(Amino-((4-aminophenyl)thio)methylene)-2-(trifluoromethyl) 

benzeneacetonitrile; SL327] 

A cell-permeable, selective inhibitor of MEK (IC = 80 nM) and MEK2 (IC = 220 nM). 

50 50 

Inhibits ERK , MKK3/p38, MKK4, JNK, and PKC activities only at higher concentrations 

(IC > 0 mM). 

50 

MEK Inhibitor II 444938 [2-Chloro-3-(N-succinimidyl)-1,4-naphthoquinone] 

A cell-permeable, potent, and selective inhibitor of MEK (IC 50 = 380 nM for MEK ). 

N MK2a Inhibitor 475863 [CMPD1; 4-(2´-Fluorobiphenyl-4-yl)-N-(4-hydroxyphenyl)-butyramide; Mitogen-activated 

protein kinase-activated protein kinase 2a Inhibitor] 

A p-amidophenolic compound that selectively inhibits the phosphorylation of MK2a 

app (mitogen-activated protein kinase-activated protein kinase 2a; K = 330 nM) by p38a 

i 

in a non-ATP-competitive manner. Does not block the kinase activity of p38a towards 

the other two known p38 substrates, MBP and ATF-2. 

InSolution ML 3 63 475800 {4-[5-(4-Fluorophenyl)-2-(4-methanesulfinyl-benzylsulfanyl)-3H-imidazol-4-yl]pyridine} 

Supplied as a 0 mM ( mg/236 ml) solution in DMSO. A cell-permeable inhibitor that 

combines the structural features of cytokine release inhibitors SKF-86002 (Cat. No. 

567305) and p38 MAP kinase inhibitor SB 203580 (Cat. No. 559389). Occupies the ATP 

binding site of p38 MAP kinase and inhibits its activity (IC 50 = 4.0 mM). 

p38 MAP Kinase 


p38 MAP Kinase 

Inhibitor III 

N InSolution p38 MAP 

Kinase Inhibitor III 

506126 [2-(4-Chlorophenyl)-4-(4-fluorophenyl)-5-pyridin-4-yl-1,2-dihydropyrazol-3-one] 

A potent p38 MAP kinase inhibitor (IC 50 = 35 nM). 

506121 {(RS)-{4-[5-(4-Fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]pyridin-2-yl}- 

(1-phenylethyl)amine]; ML3403} 

A cell-permeable, potent, selective, and ATP-competitive inhibitor of p38 MAP kinase 

(IC = 380 nM for p38a). 

50 

506148 A 0 mM ( mg/247 ml) solution of p38 MAP Kinase Inhibitor III (Cat. No. 506 2 ) 

in DMSO. 

NPPB 484100 5-Nitro-2-(3-phenylpropylamino)benzoic Acid 

Blocks phosphorylation and activation of ERK /2 and JNK/SAPK, but not p38. 

PD 98059 513000 (2´-Amino-3´-methoxyflavone) 

A potent and selective MEK inhibitor. It selectively blocks the activation of MEK, 

thus preventing its phosphorylation by c-Raf or MEK kinase (IC 50 = 2–7 mM). 

PD 693 6 513030 [4-(4-Fluorophenyl)-2-(4-nitrophenyl)-5-(4-pyridyl)-1H-imidazole] 

A potent and selective p38 MAP kinase inhibitor (IC 50 = 89 nM). 

SB 202 90 559388 [FHPI; 4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] 

A potent, selective, and cell-permeable p38 MAP kinase inhibitor (IC 50 = 50 nM for 

SAPK2a/p38 and 00 nM for SAPK2b/p38b2). 

500 mg $207 

mg $ 5 

26 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

mg 

5 mg 

$95 

$335 

$84 

$294 

5 mg $79 

5 mg $ 63 

mg $ 0 

500 mg $98 

mg $ 2 

mg $ 2 

0 mg $62 

5 mg $88 

mg $98 

mg $98 

InSolution SB 202 90 559397 A mg/ml solution of SB 202 90 (Cat. No. 559388) in anhydrous DMSO. ml $ 04 

SB 202 90, 

Immobilized 

559403 An immobilized form of the p38 MAP kinase inhibitor (Cat. No. 559388) covalently 

attached to hydrophilic acrylic beads via a 3-carbon spacer. Useful for affinityprecipitation 

of p38 MAP kinase and other functionally related proteins from cell 

or tissue extracts. 

set $ 32





SB 202474 559387 [4-Ethyl-2(p-methoxyphenyl)-5-(4´-pyridyl)-IH-imidazole] 

A negative control for MAP kinase inhibition studies. 

SB 202474, 


559407 [4-Ethyl-2(p-methoxyphenyl)-5-(4´-pyridyl)-IH-imidazole, DiHCl] 

A water-soluble form of SB 202474 (Cat. No. 559387), that serves as a negative control 

compound for SB 202 90 (Cat. No. 559388) and SB 203580 (Cat. No. 559389) in p38 

MAP kinase inhibition studies. 

SB 203580 559389 [4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] 

A potent, selective, and cell-permeable p38 MAP kinase inhibitor (IC 50 = 50 nM for 

SAPK2a/p38 and 500 nM for SAPK2b/p38b2). 

mg $ 00 

mg $ 3 

mg $98 

InSolution SB 203580 559398 A mg/ml solution of SB 203580 (Cat. No. 559389) in anhydrous DMSO. ml $ 6 

SB 203580, Iodo- 559400 [4-(3-Iodophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] 

A highly specific and potent inhibitor of p38 MAP kinase, similar to SB 203580 (Cat. No. 

559389). Useful for the identification of inhibitor binding sites of p38 MAP kinase. 

SB 203580, Sulfone 559399 [4-(4-Fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole] 

The sulfone analog of SB 203580 (Cat. No. 559389). Potently inhibits p38 MAP kinase 

(IC 50 = 30 nM). 

SB 220025 559396 [5-(2-Amino-4-pyrimidinyl)-4-(4-fluorophenyl)-1-(4-piperidinlyl)imidazole] 

A potent and specific inhibitor of human p38 MAP kinase (IC 50 = 60 nM). Displays 2000-fold 

greater selectivity for p38 MAPK over ERK (p42/p44 MAP kinase). 

SB 239063 559404 [trans-1-(4-Hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)imidazole] 

A potent MAP kinase inhibitor (IC 50 = 44 nM for inhibition of recombinant purified 

human p38a). 

SC-68376 565625 [2-Methyl-4-phenyl-5-(4-pyridyl)oxazole] 

A potent and selective inhibitor of p38 MAP kinase (IC 50 = 2–5 mM). 

SKF-86002 567305 {6-(4-Fluorophenyl)-2,3-dihydro-5-(4-pyridyl)imidazo[2,1-b]thiazole} 

A cytokine-suppressive anti-inflammatory drug (CSAID) that acts as a specific p38 MAP 

kinase inhibitor. Also inhibits cyclooxygenase and 5-lipoxygenase. 

U0 24 662006 [1,4-Diamino-2,3-dicyano-1,4-bis(methylthio)butadiene] 

A useful negative control for MEK inhibitors U0 25 (Cat. No. 662008) and U0 26 

(Cat. No. 662005). 

U0 25 662008 [1,4-Diamino-2,3-dicyano-1,4-bis(phenylthio)butadiene] 

A potent and specific inhibitor of MEK and MEK2. About 0-fold less potent than 

U0 26 (Cat. No. 662005). 

U0 26 662005 [1,4-Diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] 

A potent and specific inhibitor of MEK (IC 50 = 72 nM) and MEK2 (IC 50 = 58 nM). 

ZM 336372 692000 {N-[5-(3-Dimethylaminobenzamido)-2-methylphenyl]-4-hydroxybenzamide} 

A potent, specific and competitive inhibitor of c-Raf (IC 50 = 70 nM) that also inhibits 

p38a (IC 50 = 2 mM) and p38b2 (IC 50 = 2 mM). 

mg $ 00 

mg $98 

500 mg $ 45 

500 mg $ 06 

mg $ 8 

5 mg $ 23 

mg $68 

mg $68 

mg $66 

mg $ 27 


Phone 800 628 8470 


27



MAP Kinase Cascade Inhibitor Set 

Each set contains mg each of FPT Inhibitor III (Cat. No. 344 54) and 

ZM336372 (Cat. No. 692000), 5 mg of PD 98059 (Cat. No. 5 3000), and 

mg of SB 203580 (Cat. No. 559389). 

Cat. No. 444185 1 set $289 

MAP Kinase Inhibitor Set I 

Each set contains 5 mg of the MEK inhibitor PD 98059 (Cat. No. 

5 3000), mg each of the MAP kinase inhibitors SB 202 90 (Cat. No. 

559388) and SB 203580 (Cat. No. 559389), and mg of the negative 

control, SB 202474 (Cat. No. 559387). 

Cat. No. 444180 1 set $293 

MAP Kinase Inhibitor Set II 

Each set contains 5 mg of PD 98059 (Cat. No. 5 3000), mg each of 

SB 203580 (Cat. No. 559389) and U0 26 (Cat. No. 662005), and mg 

of the negative control, SB 202474 (Cat. No. 559387). 

Cat. No. 444190 1 set $255 

MEK Inhibitor Set 

Each set contains 5 mg of PD 98059 (Cat. No. 5 3000), mg of U0 26 

(Cat. No. 662005), and mg of the negative control U0 24 (Cat. No. 

662006). 

Cat. No. 453710 1 set $180 

To view all MAP Kinase research-related products and to request your free 

MAP Kinase wall poster, visit our MAP Kinase Interactive Pathways at: 

www.calbiochem.com/mapk 

28 Orders Phone 800 854 34 7 


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Myosin Light Chain Kinase (MLCK) Inhibitors 

Myosin light chain kinase (MLCK), a Ca 2+ -calmodulin 

dependent multi-functional enzyme, plays a critical 

role in the regulation of smooth muscle contraction and 

cellular migration. It regulates the contractile interaction 

between actin microfilaments and conventional smooth 

muscle and non-muscle myosin II. MLCK is composed of 

an N-terminal actin-binding domain, a central kinase 

domain, and a C-terminal myosin-binding domain. The 

kinase domain activates the interaction of smooth-muscle 

myosin with actin by phosphorylating the myosin light 

chain. MLCK phosphorylates a specific site on the Nterminus 

of the regulatory light chain of myosin II. This 

phosphorylation is responsible for coupling increased Ca 2+ 

concentration with smooth muscle contraction. 

In the presence of Ca 2+ , the C-terminal domain of 

calmodulin binds to the N-terminus of the calmodulinbinding 

sequence of MLCK followed by the binding 

Myosin Light Chain Kinase (MLCK) Inhibitors 



of the N-terminal domain to the C-terminus of the 

calmodulin-binding sequence. MLCK is reported to 

bind the actin filament in a manner that also allows the 

simultaneous binding of the other major thin filament 

components; calponin, tropomyosin, etc. The binding site 

is suggested to be on the outside of sub-domain 1. There 

is approximately one MLCK molecule for every 100 actin 

molecules in smooth muscle and each MLCK contains at 

least three of the DFRXXL motifs allowing each molecule 

to bind three actins (K d = 4 mM). 

References: 

Kamm, K.E., and Stull, J.T. 200 . J. Biol. Chem. 276, 4527. 

Hatch, V., et al. 200 . J. Cell Biol. 154, 6 . 

Smith, L., and Stull, J.T. 2000. FEBS let. 480, 298. 

Le, L-H., et al. 999. Proc. Natl. Acad. Sci. USA 96, 6666. 

Sellers, J.R., and Pato, M.D. 984. J.Biol.Chem. 259, 7740. 



A shorter alkyl chain derivative of W-7 (Cat. No. 68 629) that inhibits MLCK 

(K i = 7.4 mM), CK I (K i = 80 mM), CK II (K i = 5. mM), PKA (K i = 4.3 mM), PKC (K i = 47 mM), 

and PKG (K i = 3.8 mM). 

Gö 7874, Hydrochloride 365252 A potent and selective inhibitor of protein kinase C (IC 50 = 4 nM for rat brain PKC). 

Inhibits protein kinase A (IC 50 = 5 0 nM), protein kinase G (IC 50 = 4.8 mM), and myosin 

light chain kinase (IC 50 = 20 nM) at much higher concentrations. 


sp. 



K-252b, Nocardiopsis 

sp. 

420298 A cell-permeable inhibitor of MLCK (K i = 7 nM), CaM kinase II (K i = .8 nM), PKC 

(K i = 25 nM), and PKG (K i = 20 nM). Also acts as a potent inhibitor (IC 50 = 3 nM) of the 

protein tyrosine kinase activity of the NGF receptor gp 40 trk . 

0 mg $90 

500 mg $ 00 

00 mg $ 33 


420319 A non-selective inhibitor of MLCK (K i = 47 nM), PKA (K i = 90 nM), PKC (K i = 20 nM), 

and PKG (K i = 00 nM). 

ML-7, Hydrochloride 475880 [1-(5-Iodonaphthalene-1-sulfonyl)homopiperazine, HCl] 

A cell-permeable, potent and selective inhibitor of MLCK (K i = 300 nM). 

Inhibits PKA (K i = 2 mM) and PKC (K i = 42 mM) at much higher concentrations. 

ML-9, Hydrochloride 475882 [1-(5-Chloronaphthalene-1-sulfonyl)homopiperazine, HCl] 

A cell-permeable inhibitor of MLCK (K i = 3.8 mM), PKA (K i = 32 mM), and 

PKC (K i = 54 mM). 

Myosin Light Chain 

Kinase Inhibitor Peptide 

8 

475981 (H-RKKYKYRRK-NH 2 ; MLCK Inhibitor Peptide 18) 

A highly basic nonapeptide that acts as a selective inhibitor of MLCK (IC 50 = 50 nM). 

Does not block calmodulin (CaM) or inhibit the activities of CaM Kinase II or PKA. 

Piceatannol 527948 (trans-3,3´,4,5´-Tetrahydroxystilbene) 

A plant metabolite that preferentially inhibits the activity of p72 Syk (IC 50 ~ 0 mM). 

Also acts as an inhibitor of rat liver PKA catalytic subunit (IC 50 = 3 mM), PKC 

(IC 50 = 8 mM), and MLCK (IC 50 = 2 mM). 

Staurosporine, 

Streptomyces sp. 

More online... www.calbiochem.com/inhibitors/MLCK 

569397 A potent, cell-permeable broad-spectrum inhibitor of protein kinases. Inhibits MLCK 

(IC 50 = .3 nM), CaM kinase (IC 50 = 20 nM), PKA (IC 50 = 7 nM), PKC (IC 50 = 700 pM), 

and PKG (IC 50 = 8.5 nM). 

50 mg 

00 mg 

$76 

$ 33 

mg $99 

mg $99 

5 mg $ 6 

00 mg 

250 mg 

mg $4 

$ 43 

$302 


Phone 800 628 8470 


29


Myosin Light Chain Kinase (MLCK) Inhibitors, continued 


W-5, Hydrochloride 681625 [N-(6-Aminohexyl)-1-naphthalenesulfonamide, HCl] 

Calmodulin antagonist that inhibits myosin light chain kinase (IC 50 = 230 mM) and 

Ca 2+ -calmodulin-dependent phosphodiesterase (IC 50 = 240 mM). 

W-7, Hydrochloride 681629 [N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, HCl] 

A cell-permeable calmodulin antagonist that inhibits myosin light chain kinase 

(IC 50 = 5 mM) and Ca 2+ -calmodulin-dependent phosphodiesterase (IC 50 = 28 mM). 

W- 2, Hydrochloride 681635 [N-(4-Aminobutyl)-2-naphthalenesulfonamide, HCl] 



W- 3, Hydrochloride 681636 [N-(4-Aminobutyl)-5-chloro-2-naphthalenesulfonamide, HCl] 



mg $77 

0 mg $77 

mg $77 

mg $77 

30 Orders Phone 800 854 34 7 


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Phosphatidylinositol 3-Kinase (PI 3-Kinase) Inhibitors 

The PI 3-kinases are ubiquitous, heterodimeric enzymes 

that play a pivotal role in the regulation of many cellular 

processes, including motility, proliferation, and survival, 

and carbohydrate metabolism. They are dual-specificity 

enzymes capable of phosphorylating phosphoinositides. 

PI 3-kinases are divided into three classes. Class I 

kinases were the first to be characterized and include 

receptor regulated heterodimeric enzymes consisting of 

a 110 kDa catalytic subunit and an 85 kDa regulatory 

subunit (p85/p110a; p85/p110b; p101/P110g). They can 

use PI, PI (4)P, and PI (4,5)P 2 as substrates in vitro. The 

major substrate in vivo appears to be PI(4,5)P 2 . The 

members of this class are sensitive to wortmannin. Class 

II PI 3-kinases can phosphorylate PI and PI(4)P in vitro 

and show variable responses to wortmannin. This class 

of enzymes contains a C-2 domain at the C-terminal 

region that binds phospholipids in a Ca 2+ -dependent 

manner. They participate in integrin signaling in 

platelets. Class III PI 3-kinases include Vps34 that can 

phosphorylate PI(3)P. The human homologue of Vps34 is 

reported to be sensitive to wortmannin and participates 

in the regulation of endocytic membrane trafficking. 

Activated PI 3-kinase phosphorylates phosphoinositol 

(PI) substrates to produce PI(3)P, PI(3,4)P 2 , and PI(3,4,5)P 3 . 

Phosphatidylinositol 3-Kinase (PI 3-kinase) Inhibitors 




ET- 8-OCH 3 341207 (Edelfosine; 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphorylcholine) 

A non-selective weak inhibitor of PI 3-kinase (IC 50 = 35 mM). 

These molecules act as second messengers and recruit 

the PI 3-K-dependent serine/threonine kinases 

(PDK1) and Akt from the cytoplasm to the plasma 

membrane. Lipid binding and membrane translocation 

lead to conformational changes in Akt, which gets 

phosphorylated on Thr 308 in the activation loop, and 

Ser 473 in the hydrophobic phosphorylation motif by 

PDK1. This dual phosphorylation causes full activation 

of the enzyme. Inhibitors of PI 3-kinase and overexpression 

of dominant negative PI 3-kinase mutants are 

shown to block many of the physiological responses of a 

cell to insulin, indicating that PI 3-kinase lies upstream 

of these events. PI 3-kinase is becoming an attractive 

target for drug development, particularly in the areas 

of cancer and other proliferative diseases as well as 

in the treatment of inflammatory and immunological 

conditions. 

References: 

Scheid, M.P., and Woodgett, J.R. 2003. FEBS Lett. 546, 08. 

Lawlor M.A., and Alessi, D.R. 200 . J. Cell Sci. 114, 2903. 

Toker, A., and Newton, A.C. 2000. J. Biol. Chem. 275, 827 . 

Stein, R.C, and Waterfield, M.D. 2000. Mol. Med. Today 6, 347. 

Dong, Z., et al. 999. Anticancer Res. 19, 3743. 

Prior, I.A., and Clague, M.J. 999. Mol. Cell Biol. Res. Commun. 1, 62. 

More online... www.calbiochem.com/inhibitors/PI3K 

LY 294002 440202 [2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] 

A cell-permeable, potent and specific inhibitor of PI 3-kinase that acts on the ATP- 

binding site of the enzyme (IC 50 = .4 mM). Also inhibits non-homologous DNA end-joining 

in the 460 kDa PI 3-like kinase DNA-PKcs, which is the catalytic subunit of DNAactivated 

protein kinase. 

InSolution LY 294002 440204 [2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] 

A 0 mM ( mg/325 ml) solution of LY 294002 (Cat. No. 440202) in anhydrous DMSO. 

LY 3035 440203 (2-Piperazinyl-8-phenyl-4H-1-benzopyran-4-one) 

A negative control for the PI 3-kinase inhibitor, LY 294002 (Cat. No. 440202). 

Contains a single atom substitution in the morpholine ring compared to LY 294002. 

Does not affect PI 3-kinase activity even at concentrations ≥ 00 mM. 

N PI 3-Kg Inhibitor 528106 [5-Quinoxalin-6-ylmethylene-thiazolidine-2,4-dione] 

A cell-permeable, potent, selective and ATP-competitive inhibitor of PI 3-Kg 

(K i = 7.8 nM; IC 50 = 8 nM, 60 nM, 270 nM, and 300 nM for p 0-g, a, b and d-isoforms, 

respectively), while exhibiting no detectable effect against a wide panel of kinases, 

receptors, enzymes, and ion channels even at concentrations as high as mM. 

5 mg $80 

5 mg $ 24 

mg $43 

mg $99 

5 mg $ 39 


Phone 800 628 8470 


3


Phosphatidylinositol 3-Kinase (PI 3-kinase) Inhibitors, continued 


N PI 3-Kg Inhibitor II 528108 5-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethylene)-thiazolidine-2,4-dione 

A cell-permeable thiazolidinedione compound that acts as a potent and ATP-competitive 

inhibitor of PI 3-Kg (K i = 80 nM; IC 50 = 250 nM). Exhibits great selectivity over 

PI 3-Ka (IC50 = 4.5 µM), PI 3-Kb and d (IC 50 > 20 µM), and shows little effect towards 

a large panel of receptors, unrelated enzymes, ion channels, and 38 commonly studied 

kinases. 

Quercetin, Dihydrate 551600 (3,3´,4´,5,7-Pentahydroxyflavone) 

An inhibitor of PI 3-kinase (IC 50 = 3.8 mM) and phospholipase A 2 (IC 50 = 2 mM). 

Also inhibits mitochondrial ATPase, phosphodiesterases, and PKC. 

Wortmannin 681675 (KY 12420) 

A fungal metabolite that acts as a potent, selective, cell-permeable and irreversible 

inhibitor of PI 3-kinase in purified preparations and cytosolic fractions (IC 50 = 5 nM). 

Blocks the catalytic activity of PI 3-kinase without affecting the upstream signaling 

events. 

Call us or visit 

our website 

5 mg $ 35 

00 mg $33 

mg $76 

www.calbiochem.com/kinasekits 

32 Orders Phone 800 854 34 7 


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Protein Kinase A (PKA; cAMP-Dependent Protein Kinase) Inhibitors 

The cAMP-dependent protein kinase (protein kinase 

A; PKA) pathway is one of the most versatile signaling 

pathways in eukaryotic cells. Various extracellular 

signals converge on this signaling pathway through 

ligand binding to G protein-coupled receptors. Hence, 

the PKA pathway is tightly regulated at several levels to 

maintain specificity in the multitude of signal inputs. 

PKA is composed of two regulatory and two catalytic 

subunits. In the holoenzyme, the regulatory subunits 

are bound to the active site of the catalytic subunits, 

inactivating them. Binding of cAMP to the regulatory 

subunits causes a conformational change that releases 

and activates the two catalytic subunits. The active 

catalytic subunits can then phosphorylate serine and/or 

threonine residues on the substrates in the cytosol and 

in the nucleus. When the levels of cAMP begin to fall, 

the regulatory subunits regain their affinity towards the 

catalytic subunits and form the inactive holoenzyme. If 

cAMP levels remain persistently elevated, many cells 

change their behavior and may either differentiate, 

proliferate, or undergo apoptosis. 

PKA holoenzyme exists in two forms, type I and 

type II. They contain identical catalytic subunits; 

however, their regulatory subunits differ (RI or RII 

dimer). Type I holoenzyme is predominantly cytosolic, 

whereas type II holoenzyme is compartmentalized to 

subcellular organelles via specific anchoring proteins. 

The turnover rate of free type I regulatory subunit 

is significantly higher than that of type II subunits. 

When free catalytic subunit is microinjected into the 

cytoplasm of intact cells, it migrates to the nucleus, 

whereas the free regulatory subunit remains only in 

the cytoplasm following microinjection. When both 

subunits are co-injected, the regulatory subunit blocks 

the nuclear migration of the catalytic subunit. CREB 

is a major nuclear target for the catalytic subunit that 

binds to cAMP response elements (CREs) in the promoter 

regions of cAMP-responsive genes. Phosphorylation of 

CREB proteins alters their ability to form dimers and to 

interact with CREs. 

References: 

Protein Kinase A (PKA; cAMP-Dependent Protein Kinase) Inhibitors 

Skålhegg, B.S. et al. 2005. Curr. Drug Targets. 6, 655. 

Tasken, K, and Aandahl, E.M. 2004. Physiol. Rev. 84, 37. 

Taylor, S.S., et al. 2004. Biochim. Biophys. Acta 1697, 259. 

Skålhegg, B.S., and Tasken, K. 2000. Front. Biosci. 5, 678. 

Spaulding, S.W. 993. Endocrine Rev. 14, 632. 



A shorter alkyl chain derivative of W-7 (Cat. No. 68 629) that inhibits PKA 

(K i = 4.3 mM),) casein kinase I (K i = 80 mM), casein kinase II (K i = 5. mM), MLCK 

(K i = 7.4 mM), PKC (K i = 47 mM), and PKG (K i = 3.8 mM). 

Adenosine 3´,5´-cyclic 

Monophosphorothioate, 

Rp-Isomer, 

Triethylammonium Salt 



8-Bromo-, Rp-Isomer, 

Sodium Salt 



8-Bromo-2´monobutyryl-, 

Rp- 

Isomer, Sodium Salt 



8-Chloro-, Rp-Isomer, 

Sodium Salt 

More online... www.calbiochem.com/inhibitors/PKA 

116814 (Adenosine 3´,5´-cyclic Phosphorothioate-Rp; Rp-cAMPS, TEA) 

A cell-permeable inhibitor of protein kinase A (K i = mM). Resistant to hydrolysis 

by phosphodiesterases. 

116816 (Rp-8-Br-cAMPS, Na) 

A potent, cell-permeable, metabolically-stable cAMP antagonist that inhibits cAMPdependent 

protein kinase and shows preference for PKA type I. More lipophilic than 

cAMP antagonist Rp-cAMPS (Cat. No. 68 4). 

116813 (Rp-8-Br-MB-cAMPS, Na) 

An inhibitor of PKA that also inhibits the basal Ca 2+ -currents in smooth muscle. 

Reported to block the excitatory effect of 8-Bromo-cGMP (Cat No. 68 6). 

More lipophilic and cell-permeable than Rp-8-Br-cAMPS. 

116819 (Rp-8-Cl-cAMPS, Na) 

A cell-permeable, metabolically stable cAMP analog that acts as a competitive inhibitor 

of PKA. Preferentially inhibits type I PKA (IC 50 ~50 mM). 

0 mg $90 

5 mmol $ 92 

5 mmol $422 

5 mmol $524 

5 mmol $486 


Phone 800 628 8470 


33


Protein Kinase A (PKA; cAMP-Dependent Protein Kinase) Inhibitors, continued 




2´-O-Monobutyryl-, 

Rp-Isomer, Sodium Salt 

4-Cyano-3methylisoquinoline 

116825 (Rp-MB-cAMPS, Na) 

A cell-permeable precursor of Rp-cAMPS (Cat. No. 68 4), a PKA inhibitor. 

Rp-MB-cAMPS is cleaved by intracellular esterases to release butyrate and Rp-cAMPS. 

The Rp-cAMPS binds to the cAMP binding site on PKA type I and type II, thereby 

preventing holoenzyme dissociation and PKA activation. 

238900 A potent, cell-permeable, specific inhibitor of PKA (IC 50 = 30 nM). Inhibition is 

competitive with respect to ATP. 

Daphnetin 268295 (7,8-Dihydroxy-2H-1-benzopyran-2-one; 7,8-Dihydroxycoumarin) 

A coumarin analog that acts as an inhibitor of several protein kinases. Inhibits EGFR 

kinase (IC 50 = 7.67 mM), PKA (IC 50 = 9.33 mM), and PKC (IC 50 = 25 mM), in vitro. 

Ellagic Acid, Dihydrate 324683 (4,4´,5,5´,6,6´-Hexahydroxydiphenic Acid 2,6,2´,6´-Dilactone) 

A potent antioxidant that acts as a potent inhibitor of PKA catalytic subunit 

and PKC (IC 50 = 2 and 8 mM respectively). Also inhibits DNA topoisomerases I and II 

(IC 50 = .8 mM and 2. mM, respectively). 

H-7, Dihydrochloride 371955 [1-(5-Isoquinolinesulfonyl)-2-methylpiperazine, 2HCl] 

A broad based serine-threonine kinase inhibitor. Potent inhibitor of MLCK (K i = 97 mM), PKA 

(K i = 3.0 mM), PKC (K i = 6 mM), and PKG (K i = 5.8 mM). Not available for sale in Japan. 

H-8, Dihydrochloride 371958 {N-[2-(Methylamino)ethyl]-5-isoquinolinesulfonamide, 2HCl} 

Highly active inhibitor of cyclic-nucleotide-dependent protein kinases. Inhibits MLCK 

(K i = 68 mM), PKA (K i = .2 mM), PKC (K i = 5 mM), and PKG (K i = 480 nM). Not available 

for sale in Japan. 

H-9, Dihydrochloride 371961 [N-(2-Aminoethyl)-5-isoquinolinesulfonamide, 2HCl] 

Closely resembles H-8 in its chemical structure and inhibition potency. Inhibits PKA 

(K i = .9 mM), PKC (K i = 8 mM), and PKG (K i = 870 nM). Useful as a ligand for the 

separation and purification of these three enyzmes. Not available for sale in Japan. 


A cell-permeable, selective and potent inhibitor of PKA (K i = 48 nM). Inhibits other 

kinases at several fold higher concentrations: MLCK (K i = 28.3 mM), CaM kinase II 

(K i = 29.7 mM), PKC (K i = 3 .7 mM), casein kinase I (K i = 38.3 mM), and Rho Kinase II 

(IC 50 = 270 nM). Not available for sale in Japan. 

InSolution H-89, 


HA 004, 


HA 077, 



sp. 



K-252b, 


371962 {N-[2-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl} 

A 0 mM ( mg/ 93 ml) solution of H-89, Dihydrochloride (Cat. No. 37 963) in 

anhydrous DMSO. Not available for sale in Japan. 


A novel intracellular Ca 2+ -antagonist that inhibits CaM Kinase II (K i = 3 mM), 

MLCK (K i = 50 mM), PKA (K i = 2.3 mM), PKC (K i = 40 mM), and PKG (K i = .3 mM). 


371970 [Fasudil; (5-Isoquinolinesulfonyl)homopiperazine, 2HCl] 

Cell-permeable Ca 2+ -antagonist that inhibits PKA (IC 50 = .6 mM), PKG (IC 50 = .6 mM), 

and MLCK (IC 50 = 3.6 mM). Also reported to potently inhibit Rho-associated kinase. 

420298 A cell-permeable inhibitor of CaM kinase II (K i = .8 nM), MLCK (K i = 7 nM), PKA 

(K i = 8 nM), PKC (K i = 25 nM), and PKG (K i = 20 nM). Also acts as a potent inhibitor 

(IC 50 = 3 nM) of the tyrosine protein kinase activity of the NGF receptor gp 40 trk , the 

product of the trk proto-oncogene. 

5 mmol $452 

mg $95 

0 mg $50 

500 mg $57 

34 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

mg 

5 mg 

$84 

$327 

$84 

$327 

mg $84 

mg $84 

mg $84 

mg $57 

mg $84 

00 mg $ 33 

420297 A mM ( 00 mg/2 4 ml) solution of K-252a (Cat. No. 420298) in DMSO. 00 mg $ 28 



KT5720 420320 Prepared by a chemical modification of K-252a (Cat. No. 420298). Potent specific 

cell-permeable inhibitor of PKA (K i = 56 nM) that does not significantly affect the 

activity of PKC, PKG, or MLCK. 

InSolution KT5720 420323 A 2 mM (50 mg/47 ml) solution of KT5720 (Cat. No. 420320) in anhydrous DMSO. 50 mg $76 



Also inhibits rat liver PKA catalytic subunit (IC 50 = 3 mM), PKC (IC 50 = 8 mM), 

MLCK (IC 50 = 2 mM), and wheat embryo Ca 2+ /dependent protein kinase (IC 50 = 9 mM). 

50 mg 

00 mg 

50 mg 

00 mg 

$76 

$ 33 

$76 

$ 33 

mg $4

Protein Kinase A (PKA; cAMP-Dependent Protein Kinase) Inhibitors, continued 




Protein Kinase A 

Inhibitor 5-24 


Inhibitor 6-22 Amide 


Inhibitor 4-22 Amide, 


Myristoylated 



InSolution 



116805 (H-TTYADFIASGRTGRRNAIHD) 

Peptide corresponding to the active site on the skeletal muscle inhibitor protein. 

Competitive inhibitor of PKA (K i = 2.3 nM). 

539684 (PKI 6-22 Amide, PKA Inhibitor; TYADFIASGRTGRRNAI-NH 2 ) 

A potent and competitive inhibitor of PKA (K i = .7 nM). 

476485 (Myr-GRTGRRNAI-NH 2 ; Myristoylated Protein Kinase A Inhibitor Amide 14-22, 

Cell-Permeable; PKI 14-22 Amide, Cell-Permeable) 

A heat-stable protein kinase inhibitor (PKI) peptide sequence ( 4-22) that has been 

myristoylated at the N-terminus, enhancing its cell-permeability. The non-myristoylated 

version of this peptide is shown to be a highly specific inhibitor of PKA (K i = 36 nM). 

569397 A potent, cell-permeable broad spectrum inhibitor of protein kinases. Inhibits CaM 

kinase (IC 50 = 20 nM), MLCK (IC 50 = .3 nM), PKA (IC 50 = 7 nM), PKC (IC 50 = 0.7 nM), 

and PKG (IC 50 = 8.5 nM). 

569396 A mM ( 00 mg/2 4 ml) solution of Staurosporine, Streptomyces sp. 

(Cat. No. 569397) in anhydrous DMSO. 

TX- 23 655200 [2-((3,5-di-tert-Butyl-4-hydroxyphenyl)-methylene)-4-cyclopentene-1,3-dione] 

A cell-permeable inhibitor of PKA (IC 50 = 9.6 mM). Also acts as an inhibitor of Src, 

and eEF2-K (IC 50 = 2.2 and 3.2 mM, respectively). 

 

500 mg $ 24 

mg $ 08 

500 mg $84 

00 mg 

250 mg 

$ 43 

$302 

00 mg $ 43 

0 mg $90 


Phone 800 628 8470 


35


Protein Kinase C (PKC) Inhibitors 

Protein kinase C (PKC), a ubiquitous, phospholipiddependent 

enzyme, is involved in signal transduction 

associated with cell proliferation, differentiation, and 

apoptosis. At least eleven closely related PKC isozymes 

have been reported that differ in their structure, 

biochemical properties, tissue distribution, subcellular 

localization, and substrate specificity. They are 

classified as conventional (a, b1, b2, g), novel (d, e, h, 

θ, m), and atypical (z, l) isozymes. Conventional PKC 

isozymes are Ca 2+ -dependent, while novel and atypical 

isozymes do not require Ca 2+ for their activation. All PKC 

isozymes, with the exception of z and l, are activated 

by diacylglycerol (DAG). PKC isozymes negatively 

or positively regulate critical cell cycle transitions, 

including cell cycle entry and exit and the G 1 and G 2 

checkpoints. 

All PKC isoforms show different distribution among 

various cells. The a, d, and z isoforms are found in all 

cells. The g isoform is found only in neuronal cells. The 

b, e, and l isoforms are found in various tissues, whereas 

h and t isoforms are predominantly found in epithelial 

and immune cells. 

In its unstimulated state, most of the PKC resides in 

the cytosol. In this state, the pseudosubstrate sequence 

of the regulatory domain of PKC interacts with the 

catalytic domain and prevents access of the substrate 

to the catalytic site. Binding of a hormone or other 

effector molecule to the membrane receptor results in 

activation of phospholipase C (PLC) or phospholipase 

A 2 (PLA 2 ) via a G-protein-dependent phenomenon. 

The activated PLC hydrolyzes phosphatidylinositol-4, 

5-bisphosphate (PIP 2 ) to produce DAG and inositol- 

1,4,5-trisphosphate (IP 3 ). The IP 3 causes the release of 

endogenous Ca 2+ that binds to the cytosolic PKC and 

exposes the phospholipidbinding site. The binding 

of Ca 2+ translocates PKC to the membrane, where it 

interacts with DAG and is transformed into a fully active 

enzyme. 

Altered PKC activity has been linked with various types 

of malignancies. Higher levels of PKC and differential 

activation of various PKC isozymes have been reported 

in breast tumors, adenomatous pituitaries, thyroid 

cancer tissue, leukemic cells, and lung cancer cells. 

Downregulation of PKC a is reported in the majority 

of colon adenocarcinomas and in the early stages of 

intestinal carcinogenesis. Thus, PKC inhibitors have 

become important tools in the treatment of cancers. The 

involvement of PKC in the regulation of apoptosis adds 

another dimension to the effort to develop drugs that 

will specifically target PKC. 

References: 

Oka, M., and Kikkawa, U. 2005. Cancer Metastasis Rev. 24, 287. 

Mailoi, E., and Fortino, V. 2004. Endocr. Relat. Cancer 11, 6 . 

Black, J.D. 2000. Front. Biosci. 5, 406. 

Cooper, D.R., et al. 999. Arch. Biochem. Biophys. 372, 69. 

Yamamoto, M., et al. 998. Exp. Cell Res. 240, 349. 

Rasmussen, H., et al. 995. Endocr. Rev. 16, 649. 

Taylor, S.S., et al. 995. FASEB J. 9, 255. 

Nishizuka, Y. 995. FASEB. J. 9, 484. 

Newton, A.C. 995. J. Biol. Chem. 270, 28495. 

Hanks, S., and Hunter, T. 995. FASEB J. 9, 576. 

Blobe, G.C., et al. 994. Cancer Metastasis Rev. 13, 4 . 

Basu, A. 993. Pharmacol. Ther. 59, 257. 

More online... www.calbiochem.com/inhibitors/PKC 

36 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Isozyme Specificities of Selected Protein Kinase C Inhibitors (IC 50 values are in µM) 



Product Cat. No. PKC a PKC b PKC bI PKC bII PKC g PKC d PKC e PKC z PKC m PKC h Ref. 

Bisindolylmaleimide I (Gö 6850) 203290 0.008 — 0.0 8 — — 0.2 0. 32 5.8 — — 

CGP4 25 — 0.024 — 0.0 7 0.032 0.0 8 0.360 4.50 > 000 — 0.060 2 

Gö 6976 365250 0.0023 — 0.006 — — — — — 0.02 — 

Gö 6983 365251 0.007 0.007 — — 0.006 0.0 — 0.06 20 — 3 

LY33353 — 0.360 — 0.0047 0.0059 0.400 0.250 0.600 > 0 5 — 0.052 4 

PKCb Inhibitor 539654 0.33 — 0.02 0.005 > .0 — 2.8 — — — 5 

Ro-3 -7549 557508 0.053 0. 95 0. 63 0.2 3 — 0. 75 — — — 6 

Ro-3 -8220 557520 0.005 — 0.024 0.0 4 0.027 — 0.024 — — — 6 

Ro-3 -8425 557514 0.008 — 0.008 0.0 4 0.0 3 — 0.039 — — — 6 

Ro-32-0432 557525 0.009 — 0.028 0.03 0.037 — 0. 08 — — — 6 

Rottlerin 557370 30 42 — — 40 3 - 6 00 00 — — 7 

Staurosporine 569397 0.028 — 0.0 3 0.0 0.032 0.028 0.025 > .5 — — 6 

UCN0 — 0.029 — 0.034 — 0.030 0.590 0.530 — — — 8 

References: 

. Martiny-Baron, G.M. et al. 993. J. Biol. Chem. 268, 9 94. 

2. Marte, B.M., et al. 994. Cell Growth Differ. 5, 239. 

3. Gschwendt, M., et al. 996. FEBS Lett. 392, 77. 

Protein Kinase C (PKC) Inhibitors 


Bisindolylmaleimide I 203290 {2-[1-(3-Dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide; 

Gö 6850; GF 109203X} 

InSolution 

Bisindolylmaleimide I 

Bisindolylmaleimide I, 

Hydrochloride 

A highly selective cell-permeable PKC inhibitor (K i = 0 nM) that is structurally similar 

to staurosporine. Acts as a competitive inhibitor for the ATP-binding site of PKC. Shows 

high selectivity for the a, bII, g, and e isozymes of PKC. May inhibit protein kinase A at a 

much higher concentration (K i = 2 mM). 

203293 {2-[1-(3-Dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide; Gö 6850} 

A mg/ml solution of Bisindolylmaleimide I (Cat. No. 203290) in anhydrous DMSO. 

203291 {2-[1-(3-Dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide, HCl} 

An inhibitor of PKC (K i = 0 nM). Inhibits PKA at much higher concentrations (K i = 2 mM). 

An enhanced water-soluble form of Bisindolylmaleimide I (Cat. No. 203290). 

Bisindolylmaleimide II 203292 {2-[1-[2-(1-Methylpyrrolidino)ethyl]-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide} 

A potent and selective inhibitor of PKC (IC 50 = 3 nM). Also inhibits PKA at much higher 

concentrations (IC 50 = 2 mM). 

Bisindolylmaleimide III, 

Hydrochloride 

203294 {2-[1-(3-Aminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide, HCl} 

A potent and selective inhibitor of PKC (IC 50 = 26 nM). It also inhibits PKA at much 

higher concentrations (IC 50 = 500 nM). 

Bisindolylmaleimide IV 203297 [Arcyriarubin A; 2,3-bis(1H-Indol-3-yl)maleimide] 

A potent and selective inhibitor of PKC (IC 50 = 87 nM) and PKA (IC 50 = 2.7 mM). 

Bisindolylmaleimide V 203303 [2,3-bis(1H-Indol-3-yl)-N-methylmaleimide; Ro 31-6045] 

Useful as a negative control compound for PKC inhibition studies (IC 50 > 00 mM). 

Blocks the activation of p70 s6k /p85 s6k in vivo (IC 50 = 8 mM). 

Calphostin C, 

Cladosporium 

cladosporioides 

Cardiotoxin, Naja 

nigricollis 

4. Jirousek, M.R., et al. 996. J. Med. Chem. 39, 2664. 

5. Tanaka, M., et al. 2004. Bioorg. Med. Chem. Lett. 14, 5 7 . 

6. Wilkinson, S.E., at al. 993. Biochem. J. 294, 335. 

7. Gschwendt, M., et al. 994. Biochem. Biophys. Res. Commun. 199, 93. 

8. Seynaeve, C.M., et al. 994. Mol. Pharmacol. 45, 207. 

208725 (UCN-1028c) 

Cell-permeable, highly specific inhibitor of PKC (IC 50 = 50 nM) that interacts with 

the protein’s regulatory domain by competing at the binding site of diacylglycerol 

and phorbol esters. At higher concentrations inhibits MLCK (IC 50 > 5 mM), PKA 

(IC 50 > 50 mM), PKG (IC 50 >25 mM), and p60 v-src protein tyrosine kinase (IC 50 > 50 mM). 

Does not compete with Ca 2+ or phospholipids. 

217504 A cytolytic toxin that causes depolarization of skeletal muscle fibers in vitro. Stimulates 

Ca 2+ transport and ATP hydrolysis by sarcolemmal Ca 2+ /Mg 2+ -ATPase. Its action is 

strongly potentiated by phospholipase A 2 . Inhibits PKC (IC 50 = .8 mM). Not available for 

sale outside of the United States. 

250 mg 

mg 

250 mg 

mg 

250 mg 

mg 

250 mg 

mg 

250 mg 

mg 

$35 

$ 03 

ml $ 07 

$35 

$ 03 

mg $ 45 

50 mg 

00 mg 

$52 

$ 42 

$49 

$ 4 

$44 

$ 4 

$8 

$ 48 

mg $ 63 


Phone 800 628 8470 


37


Protein Kinase C (PKC) Inhibitors, continued 


Chelerythrine Chloride 220285 Naturally occurring alkaloid. Cell-permeable, selective inhibitor of PKC (IC 50 = 660 nM). 

Acts on the catalytic domain irrespective of the attachment of the regulatory domain. 

A competitive inhibitor with respect to the phosphate acceptor and a non-competitive 

inhibitor with respect to ATP. Over ten-fold more potent than H-7, Dihydrochloride 

(Cat. No. 37 955). 

Dequalinium Chloride 263225 (DECA) 

An antitumor agent and PKC inhibitor. When exposed to UV light, DECA covalently and 

irreversibly inhibits PKC a or PKC b (IC 50 = 7- 8 mM). 


A potent antioxidant with anti-mutagenic and anti-carcinogenic properties. Inhibits 

DNA topoisomerases I and II (IC 50 = .8 mM and 2. mM, respectively). Acts as a potent 

inhibitor of PKA catalytic subunit and PKC (IC 50 = 2 mM and 8 mM respectively). 

Gö 6976 365250 [12-(2-Cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a) 

pyrrolo (3,4-c)-carbazole; Go 6976] 

An inhibitor of PKC (IC 50 = 7.9 nM for rat brain). Selectively inhibits Ca 2+ -dependent PKC 

a-isozyme (IC 50 = 2.3 nM) and PKC bI (IC 50 = 6.2 nM). Does not affect the kinase activity 

of the Ca 2+ -independent PKC d , PKC e , and PKC z isoenzymes even at micromolar levels. 

InSolution Gö 6976 365253 [12-(2-Cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a) 

pyrrolo (3,4-c)-carbazole; Go 6976, Solution] 

A 500 mg/ml solution of Gö 6976 (Cat. No. 365250) in anhydrous DMSO. 

Gö 6983 365251 {2-[1-(3-Dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide; 

Go 6983} 

A potent inhibitor of PKC that has been shown to selectively inhibit several PKC isozymes 

(IC 50 = 7 nM for PKC a and PKC b ; 6 nM for PKC g ; 0 nM for PKC d ; 60 nM for PKC z ). 

Gö 6983 does not effectively inhibit PKC m (IC 50 = 20 mM) and can thus be used 

to differentiate PKC m from other PKC isozymes. 

Gö 7874, Hydrochloride 365252 A potent and selective inhibitor of rat brain PKC (IC 50 = 4 nM) versus MLCK 

(IC 50 = 20 nM), PKA (IC 50 = 50 nM), and PKG (IC 50 = 4.8 mM). 


A broad based serine-threonine kinase inhibitor. Potent inhibitor of MLCK (K i = 97 mM), 

PKA (K i = 3 mM), PKC (K i = 6 mM), and PKG (K i = 5.8 mM). Not available for sale in Japan. 

Iso-H-7, 


371956 [1-(5-Isoquinolinesulfonyl)-3-methylpiperazine, 2HCl] 

Less potent than H-7 in inhibiting rat brain PKC isoforms (IC 50 = 50 mM). 

Also inhibits other cyclic-nucleotide-dependent protein kinases. 

HBDDE 372770 (2,2´,3,3´,4,4´-Hexahydroxy-1,1´-biphenyl-6,6´-dimethanol Dimethyl Ether) 

An inhibitor of PKC that selectively inhibits PKC a (IC 50 = 43 mM) and PKC g (IC 50 = 50 mM) 

over PKC d , PKC bI , and PKC bII isozymes. 

Hispidin 377980 [6-(3,4-Dihydroxystyrl)-4-hydroxy-2-pyrone] 

A potent inhibitor of PKC b isoform (IC 50 = 2 mM). 

Hypericin 400076 A polycyclic dione that inhibits PKC (IC 50 = 3.3 mM). Also known to inhibit the 

protein tyrosine kinase activities of the insulin receptor (IC 50 = 20 - 29 nM), EGFR 

(IC 50 = 35 nM), casein kinase II (IC 50 = 6 nM), and MAP kinase (IC 50 = 4 nM). 

Useful probe for PKC due to its bright red fluorescence emission and photostability. 


sp. 




sp. 

420298 A cell-permeable protein kinase inhibitor that inhibits CaM kinase II (K i = .8 nM), 

MLCK (K i = 7 nM), PKA (K i = 8 nM), PKC (K i = 25 nM), and PKG (K i = 20 nM). 

5 mg $97 

500 mg $57 

500 mg $57 

500 mg $ 22 

ml $ 36 

500 mg $89 

500 mg $ 00 

38 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

$84 

$327 

mg $87 

mg $ 38 

2 mg $ 44 

mg $ 05 

00 mg $ 33 




K-252c 420305 Inhibits PKA (IC 50 = 25.7 mM) and PKC (IC 50 = 2.45 mM). mg $ 50 

Melittin 444605 A 26-residue polypeptide from bee venom that binds calmodulin in a Ca 2+ -dependent 

manner. Activates phospholipase A 2 and inhibits protein kinase C (IC 50 = 5-7 mM) by 

binding to the catalytic domain in a Mg 2+ -ATP sensitive manner. Has also been used 

for affinity purification of several Ca 2+ -binding proteins. A stimulator of G i a and G a 

activity that is reported to inhibit adenylate cyclase activity in synaptic membranes. 

50 mg 

00 mg 

$76 

$ 33 

250 mg $67





NGIC-I 481500 (Non-glycosidic Indolocarbazole I) 

A potent and selective inhibitor of PKC (IC 50 = 75 nM) versus PKA (IC 50 > 0 mM) and PKG 

(IC 50 = 320 nM). 

Phloretin 524488 (2´,4´,6´-Trihydroxy-3-p-hydroxyphenylpropiophenone) 

A flavonoid that prevents the activation of PKC. 



Also acts as an inhibitor of the rat liver PKA catalytic subunit (cAK) (IC 50 = 3 mM), PKC 

(IC 50 = 8 mM), MLCK (IC 50 = 2 mM), and wheat embryo Ca 2+ -dependent protein kinase 

(CDPK) (IC 50 = 9 mM). 

N PKC b Inhibitor 539654 [3-(1-(3-Imidazol-1-ylpropyl)-1H-indol-3-yl)-4-anilino-1H-pyrrole-2,5-dione] 

A potent, ATP-competitive inhibitor of PKC b isozymes (IC 50 = 5 nM and 2 nM for human 

PKC bII and bI ). Displays greater selectivity over PKC a , PKC g , and PKC e (IC 50 = 33 nM, 

> mM, and 2.8 mM, respectively). 

N PKC bII /EGFR Inhibitor 539652 A cell-permeable symmetrical phthalimide compound that acts as a potent and ATPcompetitive 

inhibitor of EGFR and PKC isozymes a, bI, and bII (IC 50 = 0.7, .9, 3.8, and 

0.4 mM, respectively), while exhibiting little or much weaker activity towards a panel of 

6 other kinases, including novel and atypical PKC isozymes. Reported to inhibit insulinstimulated 

cellular 2-deoxyglucose uptake, osteoclast differentiation, ERK activation, 

and TLS/FUS DNA-binding activity in vitro, and exhibit antitumor activity in mice in vivo. 

Polymyxin B Sulfate 5291 (Aerosporin) 

An antibiotic that inhibits phospholipid sensitive Ca 2+ -dependent protein kinase. 

Mixture of polymyxin B sulfate and polymyxin B 2 sulfate. 

Protein Kinase C 

Inhibitor 20-28, 


Myristoylated 


Inhibitor, EGF-R 

Fragment 65 -658, 

Myristoylated 


Inhibitor Peptide 9-3 


Inhibitor Peptide 9-36 

Protein Kinase C h 

Pseudosubstrate 

Inhibitor, Myristoylated 

Protein Kinase C z 



Protein Kinase C z 



Protein Kinase C θ 



Protein Kinase C θ 



476480 (Myr-N-FARKGALRQ-NH 2 ; Myristoylated Protein Kinase C Inhibitor 20-28, Cell-Permeable) 

Pseudosubstrate sequence from PKC a and PKC b . N-terminal myristoylated to allow membrane 

permeability. Highly specific inhibitor of TPA activation of MARCKS phosphorylation 

in fibroblast primary cultures (IC 50 = 8 mM). Exhibits 98% inhibition at 00 mM. 

476475 [Myr-N-RKRTLRRL-OH; Myristoylated EGF-R Fragment (651-658), PKC Inhibitor] 

Epidermal growth-factor receptor (EGF-R) conserved sequence that is identical to verbB 

(95- 02). An N-terminal myristoylated membrane-permeable inhibitor that inhibits 

PKC (IC 50 = 5 mM) in intact cells. 

05-23- 

4904 

(PKC 19-31; RFARKGALRQKNV) 

More potent inhibitor of PKC (IC = 00 nM) than Protein Kinase C Inhibitor Peptide 

50 

9-36 (Cat. No. 539560). 

539560 (PKC 19-36; RFARKGALRQKNVHEVKN) 

Acts as a pseudo substrate by binding to the active sites of protein kinases. 

Potent inhibitor of PKC (K i = 47 nM) but not of PKA (IC 50 = 423 mM). 

539604 (Myr-TRKRQRAMRRRVHQING-NH 2 ) 

A cell-permeable myristoylated PKC h pseudosubstrate inhibitor of protein kinase C h 

isozyme. Useful for studies of PKC h function in intact cells. 

539610 (SIYRRGARRWRKL) 

A non-cell-permeable PKC z pseudosubstrate sequence peptide that can be used as a 

competitive inhibitor PKC z in in vitro kinase assays. 

539624 (Myr-SIYRRGARRWRKL-OH) 

A cell-permeable myristoylated form of PKC z pseudosubstrate peptide 

(Cat. No. 5396 0) that includes amino acids 3– 25 of the pseudosubstrate region. 

Useful for inhibition studies of PKC z in intact cells. 

539634 (LHQRRGAIKQAKVHHVKC-NH 2 ) 

A selective and competitive inhibitor of protein kinase C θ isozyme that includes amino 

acids 3– 25 of the pseudosubstrate sequence. 

539636 (Myr-LHQRRGAIKQAKVHHVKC-NH 2 ) 

A cell-permeable myristoylated PKC θ pseudosubstrate sequence peptide 

(Cat. No. 539634). Useful for studies of PKC θ function in intact cells. 

500 mg $ 30 

200 mg $8 

mg $4 

500 mg $ 26 

2 mg $ 3 

500 mg 

g 

5 g 

$3 

$50 

$208 

500 mg $ 03 

500 mg $ 04 

mg 

5 mg 

500 mg 

mg 

$98 

$372 

$ 33 

$238 

500 mg $ 64 

500 mg $ 7 

500 mg $ 45 

500 mg $ 23 

500 mg $ 69 


Phone 800 628 8470 


39




Protein Kinase C e 

Translocation Inhibitor 

Peptide 

Protein Kinase C e 

Translocation Inhibitor 

Peptide, Negative 

Control 

539522 (EAVSLKPT; PKC e Translocation Inhibitor Peptide) 

An octapeptide that selectively inhibits the translocation of PKC e to subcellular sites. 

Inhibition of PKC e translocation is known to specifically block phorbol ester or 

norepinephrine-mediated regulation of contraction in cardiomyocytes. 

539542 (LSETKPAV) 

A scrambled peptide with an identical amino acid composition to that of PKC e 

Translocation Inhibitor Peptide (Cat. No. 539522). Useful as a negative control for 

this PKC e translocation inhibitor. 

Ro-3 -7549 557508 {2-[1-3(Aminopropyl)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide, Acetate; 

Bisindolylmaleimide VIII, Acetate} 

Ro 3 -7549, 

Immobilized 

A selective PKC inhibitor that acts at the ATP binding site of PKC (IC 50 = 58 nM for rat 

brain PKC). IC 50 values for individual PKC isozymes are as follows: 53 nM for PKC a , 

95 nM for PKC bI , 63 nM for PKC bII , 2 3 nM for PKC g , and 75 nM for PKC e . 

557509 An immobilized form of the PKC inhibitor Ro-3 -7549 (Cat. No. 557508) that is 

covalently attached to hydrophilic acrylic beads via an 8-carbon spacer. Useful to 

affinity-precipitate PKC and other functionally related proteins from cell or tissue 

extracts. Binding capacity: ≥3 mg purified PKC a per gram of dry beads. 

Ro-3 -8220 557520 {3-[1-[3-(Amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide; 


N InSolution 

Ro-3 -8220 

A competitive, selective inhibitor of PKC (IC 50 = 0 nM) over PKA (IC 50 = 900 nM), 

CaM kinase (IC 50 = 7 mM) and phosphorylase protein kinase. 

557521 {3-[1-[3-(Amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide; 


A 5 mM (500 mg/ 8 ml) solution of Ro-3 -8220 (Cat. No. 557520) in H 2 O. 

Ro-3 -8425 557514 {2-[8-(Aminomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-3-(1-methyl-1H-indol- 

3-yl)maleimide, HCl; Bisindolylmaleimide X, HCl} 

A potent and selective inhibitor of PKC (IC 50 = 5 nM for rat brain PKC). Exhibits some 

degree of isozyme specificity (IC 50 = 8 nM for PKC a , 8 nM for PKC bI , 4 nM for PKC bII , 

3 nM for PKC g , and 39 nM for PKC e ). Shows slight selectivity for the conventional PKC 

isozymes PKC a , PKC b , and PKC g over the Ca 2+ -independent PKC isozyme PKC e . 

Ro-32-0432 557525 {Bisindolylmaleimide XI, HCl; 2-{8-[(Dimethylamino)methyl]-6,7,8,9-tetrahydropyrido 

[1,2-a]indol-3-yl}-3-(1-methyl-1H-indol-3-yl)maleimide, HCl} 

A selective cell-permeable PKC inhibitor. Displays about a 0-fold greater selectivity 

for PKC a (IC 50 = 9 nM) and a 4-fold greater selectivity for PKC bI (IC 50 = 28 nM) over PKC e 

(IC 50 = 08 nM). 

Rottlerin 557370 (Mallotoxin) 

An inhibitor of PKC d (IC 50 = 3-6 mM) and PKC θ . Also inhibits PKC a , PKC b , and PKC g 

isoforms, but with significantly reduced potency (IC 50 = 30-42 mM). Has reduced 

inhibitory activity on PKC e , PKC h , and PKC x (IC 50 = 80- 00 mM). Also known to inhibit 

CaM kinase III (IC 50 = 5.3 mM). 

Safingol 559300 (L-threo-Dihydrosphingosine) 

A lyso-sphingolipid PKC inhibitor that competitively interacts at the regulatory phorbol 

binding domain of PKC. Inhibits enzymatic activity and 3 H-phorbol dibutyrate binding of 

purified rat brain PKC (IC 50 = 37.5 mM and 3 mM, respectively). Inhibits human PKC a in 

MCF-7 DOXR cells (IC 50 = 40 mM). 

Sangivamycin 559307 (7-Deaza-7-carbamoyladenosine; NSC-65346) 

A cytotoxic purine nucleoside that acts as a selective and potent inhibitor of PKC 

(IC 50 = 0 mM). The inhibition is competitive with respect to ATP and non-competitive 

with respect to histone and lipid cofactors. 

D-erythro-Sphingosine, 

Free Base, Bovine Brain 


Free Base, High Purity 

567725 (trans-D-erythro-2-Amino-4-octadecene-1,3-diol; Ceramide; Cerebroside) 

A potent and selective inhibitor of PKC (PKC; IC 50 = 2.8 mM) and insulin receptor tyrosine 

kinase. PKC inhibition is competitive with respect to diacylglycerol, phorbol dibutyrate, 

and Ca 2+ . 

567726 (trans-D-erythro-2-Amino-4-octadecene-1,3-diol; Ceramide; Cerebroside) 

A highly purified preparation of Cat. No. 567725 containing >99% of the erythro isomer. 

A potent and selective inhibitor of PKC (IC 50 = 2.8 mM) and insulin receptor tyrosine kinase. 

PKC inhibition is competitive with respect to diacylglycerol, phorbol dibutyrate, and Ca 2+ . 

5 mg $ 56 

5 mg $ 56 

mg $95 

set $ 32 

500 mg $83 

500 mg $83 

mg $95 

40 Orders Phone 800 854 34 7 


Fax 800 776 0999 


500 mg 

mg 

$70 

$ 2 

0 mg $77 

mg $ 2 

mg $87 

0 mg $69 

0 mg $83





Dihydro- 


N,N-Dimethyl- 

N Scytonemin, Lyngbya 

sp. 

N 




300230 (Sphinganine) 

Biosynthetic precursor of sphingosine. Inhibits PKC in Chinese hamster ovary cells 

(IC 50 = 2.9 mM). 

0 mg $79 

310500 A PKC inhibitor (IC 50 = 2 mM) that also enhances src kinase activity. 5 mg $8 

565715 (SCY) 

A cell-permeable, dimeric indolo-phenol compound that acts as a selective, reversible, 

non-toxic, and mixed type inhibitor of polo-like kinase (Plk ; IC 50 = 2.0 mM) and PKC bI 

(IC 50 = 3.4 mM) and exhibits anti-proliferative and anti-inflammatory properties. Also 

inhibits several other cell cycle regulatory kinases, and PKC bII (IC 50 = .2 mM, .4 mM, 

3.0 mM, and 2.7 mM for Myt , Chk , Cdk /B, and PKC bII ). At higher concentrations, 

affects the activities of PKA and Tie2 (IC 50 > 0 mM). 

569397 A potent, cell-permeable broad spectrum inhibitor of protein kinases. Inhibits CaM 

kinase (IC 50 = 20 nM), MLCK (IC 50 = .3 nM), PKA (IC 50 = 7 nM), PKC (IC 50 = 700 pM), 

and PKG (IC 50 = 8.5 nM). 

00 mg 

250 mg 

mg $98 

Tamoxifen Citrate 579000 A potent synthetic anti-estrogen. A reversible inhibitor of PKC (IC 50 = 0 mM). 00 mg $4 

Tamoxifen, 

4-Hydroxy-, (Z)- 

579002 [(Z)-4-Hydroxytamoxifen; 4-OH-TAM] 

An active metabolite of the widely used therapeutic anti-estrogen agent, tamoxifen 

(Cat. No. 579000) that is more potent than the parent compound. Inhibits PKC by 

modifying its catalytic domain. 

TER 4687 581800 [(±)-2N,N-Dimethylaminomethyl-1-indanone, HCl] 

Blocks the association between protein kinase C θ -V and p59fyn in a yeast reporter 

assay. Prevents normal translocation of PKC θ in T cells. Has no effect on other PKC 

isozymes in Jurkat or normal T cells. 

Vitamin E Succinate 679130 (a-Tocopheryl Succinate; VES) 

Enhances the immune response and induces cellular differentiation and/or growth 

inhibition. VES has been shown to modulate adenylate cyclase and cAMP-dependent 

proteins, inhibit protein kinase C activity, bind to a cellular vitamin E binding protein, 

suppress c-myc and c-H-ras oncogene expression, and regulate TGF-b protein 

production. Also shown to induce apoptosis in RL cells. Exhibits antioxidant properties. 

Polo-like Kinase Inhibitor 

Scytonemin, Lyngbya sp. 

To view all PKC research-related products and 

to request your free PKC wall poster, visit our 

PKC Interactive Pathways at: 

www.calbiochem.com/pkc 

A cell-permeable, dimeric indolo-phenol compound that acts as a 

selective, reversible, non-toxic, and mixed type inhibitor of polo-like 

kinase (Plk ; IC 50 = 2.0 mM) and PKC bI (IC 50 = 3.4 mM) and exhibits 

anti-proliferative and anti-inflammatory properties. Also inhibits several 

other cell cycle regulatory kinases, and PKC bII (IC 50 = .2 mM, .4 mM, 

3.0 mM, and 2.7 mM for Myt , Chk , Cdk /B, and PKC bII ). At higher 

concentrations, affects the activities of PKA and Tie2 (IC 50 > 0 mM). 

Cat. No. 565715 1 mg $98 

$ 43 

$302 

5 mg $97 

0 mg $ 23 

00 mg $34 


Phone 800 628 8470 


4

N 


Protein Kinase C (PKC) Inhibitor Sets 

Bisindolylmaleimide Inhibitor Set 

Contains 250 mg each of Bisindolylmaleimide I, Hydrochloride 

(Cat. No. 20329 ), Bisindolylmaleimide II (Cat. No. 

203292), Bisindolylmaleimide III, HCl (Cat. No. 203294), 

Bisindolylmaleimide IV (Cat. No. 203297), Bisindolylmaleimide V 

(Cat. No. 203303), and RIM- (Cat. No. 557325). 

Cat. No. 203305 1 set $276 

Serine/Threonine Kinase Inhibitor Set 

A set of 6 vials. Each set contains 250 mg of PKC inhibitor, 

Bisindolylmaleimide I (Cat. No. 203290); mg of PKA inhibitor, 

H-89, Dihydrochloride (Cat. No. 37 963); mg of PKG inhibitor, 

PKG Inhibitor (Cat. No. 370654); mg of MLCK inhibitor, ML-7 

(Cat. No. 475880); mg of CaM kinase II inhibitor, KN-93 (Cat. 

No. 422708); and 00 mg of the broad range Serine/Threonine 

Kinase inhibitor, Staurosporine (Cat. No. 569397). Not available 


Cat. No. 539572 1 set $354 

Related Products 

Recombinant PKC Isozymes 

Protein Kinase C , His•Tag®



Protein Kinase G (PKG; cGMP-Dependent Protein Kinase) Inhibitors 

cGMP produces its effects by interacting with 

intracellular receptor proteins. A primary action of 

elevated cGMP levels is the stimulation of cGMPdependent 

protein kinase (PKG), which catalyzes the 

phosphorylation of a number of physiologically relevant 

proteins involved in contractile activity of smooth 

muscle cells. The mammalian PKG family consists of 

PKGIa and Ib, splice forms derived from one gene, and 

PKGII, encoded by a second gene. They are ubiquitous 

effector enzymes that regulate a variety of physiological 

processes in response to nitric oxide and natriuretic 

agonists. Cells of the cardiovascular system, such as 

fibroblasts and certain types of endothelial cells, contain 

PKGI. Smooth muscle cells are rich in PKGIa and Ib, 

platelets and T lymphocytes contain PKGIb, and cardiac 

myocytes contain PKGIa. It is important to note that 

PKGs are lost in many primary cell types upon passaging 

in cell culture and may not be detected in many cell 

lines. Studies have shown that cultured vascular smooth 

muscle cells (VSMCs) may stop expressing PKG and 

acquire a non-contractile phenotype. The restoration 

of PKG expression can result in the cells acquiring 

a more contractile phenotype. This is an important 

observation because several vascular disorders result 

from accumulation of noncontractile VSMC in the 

vessel wall. In endothelial cells PKGI phosphorylates 

and activates eNOS, which reduces its Ca 2+ -dependence. 

Also, in endothelial cells, PKGI and PKGII are known 

to phosphorylate 6-pyruvoyltetrahydropterin synthase 

to produce tetrahydrobiopterin, a required cofactor for 

eNOS activation. 

References: 

Protein Kinase G (PKG; cGMP-Dependent Protein Kinase) Inhibitors 

Feil, R., et al. 2005, Rev. Neurosci. 16, 23. 

Munzel, T., et al. 2003. Circulation 108, 2 72. 

Browning, D.D., et al. 200 . J. Biol. Chem. 276, 3039. 

Wang, X., and Robinson, P.J. 997. J. Neurochem. 68, 443. 

Lincoln, T.M., et al. 200 . J. Appl. Physiol. 91, 42 . 



A shorter alkyl chain derivative of W-7 (Cat. No. 68 629) that inhibits PKG (K i = 3.8 mM), 

casein kinase I (K i = 80 mM), casein kinase II (K i = 5. mM), MLCK (K i = 7.4 mM), PKA 

(K i = 4.3 mM), and PKC (K i = 47 mM). 

Drosophila 

Antennapedia Homeo- 

Domain (43-58) 

Guanosine 3´,5´-cyclic 


Rp-Isomer, 




8-Bromo-, Rp-Isomer, 

Sodium Salt 



8-(4-Choloro- 

phenylthio)-, Rp- 

Isomer, 




b-Phenyl- , N 2 -etheno- 

8-bromo-, Rp-Isomer, 

Sodium Salt 

More online... www.calbiochem.com/inhibitors/PKG 

287895 (DT-5; RQIKIWFQNRRMKWKK) 

The membrane translocation signal sequence from Drosophila Antennapedia homeodomain 

(43-58) that inhibits PKGIa (K i = 970 nM). Does not exhibit significant inhibition 

against PKA (K i = 07 mM). 

370666 (Rp-cGMPS, TEA) 

A competitive inhibitor of PKGIa that blocks PKG and PKA activation (K i = 20 mM). 

Exhibits low cell permeability. 

370674 (Rp-8-Br-cGMPS, Na) 

A potent, cell-permeable, metabolically stable inhibitor of PKG. Significantly more 

lipophilic and membrane-permeable than cGMP or Rp-cGMPS. Resistant to mammalian 

cyclic nucleotide-dependent phosphodiesterases. 

370677 (Rp-8-pCPT-cGMPS, TEA) 

A potent, cell-permeable inhibitor of PKG Ia, Ib, and type II. A combination of the protein 

kinase inhibitor Rp-cGMPS and the widely used cGMP analog, 8-pCPT-cGMP. Significantly 

more lipophilic and membrane-permeant than Rp-cGMPS and Rp-8-Br-cGMPS. Resistant 

to hydrolysis by mammalian cyclic nucleotide dependent phosphodiesterases. 

370679 (Rp-8-Br-PET-cGMPS, Na) 

A metabolically stable, competitive inhibitor of PKGIa and Ib (K i = 30 nM). 

Also reported to block the activation of purified PKA type II (K i = 0 mM). 

More lipophilic and cell-permeable than Rp-8-pCPT-cGMPS (Cat. No. 370677). 

0 mg $90 

mg $90 

5 mmol $348 

5 mmol $430 

mmol $2 5 

mmol $ 4 


Phone 800 628 8470 


43


Protein Kinase G (PKG; cGMP-Dependent Protein Kinase) Inhibitors, continued 



A potent inhibitor of PKG (K i = 5.8 mM), MLCK (K i = 97 mM), PKA (K i = 3.0 mM), 

and PKC (K i = 6 mM). Not available for sale in Japan. 

H-9, Dihydrochloride 371961 [N-(2-Aminoethyl)-5-isoquinolinesulfonamide, 2HCl] 

An inhibitor of PKG (K i = 870 nM), PKA (K i = .9 mM), and PKC (K i = 8.0 mM). 

Useful as a ligand for the separation and purification of these three enzymes. 


H-9, Immobilized 371966 An immobilized form of the protein kinase inhibitor H-9 (Cat. No. 37 96 ) covalently 

attached to hydrophilic acrylic beads via an 8-carbon spacer. set = 25 mg of H-9 

Immobilized beads and 25 mg of control beads. 

HA 004, 


HA 077, 



sp. 




sp. 


An inhibitor of PKG (K i = .3 mM), CaM kinase II (K i = 3 mM), MLCK (K i = 50 mM), 

PKA (K i = 2.3 mM), and PKC (K i = 40 mM). Not available for sale in Japan. 


An inhibitor of PKG (IC 50 = .6 mM), PKA (IC 50 = .6 mM), and MLCK (IC 50 = 3.6 mM). 

Also reported to potently inhibit Rho-associated kinase (ROCK). 

420298 A cell-permeable inhibitor of PKG (K i = 20 nM), CaM kinase II (K i = .8 nM), 

MLCK (K i = 7 nM), PKA (K i = 8 nM), and PKC (K i = 25 nM). 

420297 Supplied as a mM ( 00 mg/2 4 ml) solution of K-252a (Cat. No. 420298) in anhydrous 

DMSO. 

420319 An inhibitor of PKG (K i = 00 nM), MLCK (K i = 47 nM), PKA (K i = 90 nM), and PKC 

(K i = 20 nM). 

KT5823 420321 A cell-permeable, highly specific inhibitor of PKG (K i = 234 nM). Inhibits PKC 

(K i = 4.0 mM) and PKA (K i > 0.0 mM) at higher concentrations. 

Protein Kinase G 


Protein Kinase G 

Ia Inhibitor, 




370654 (PKG Inhibitor; RKRARKE) 

A specific inhibitor of PKG (K i = 86 mM) relative to PKA (K i = 550 mM). Sequence corresponds 

to a non-phosphorylatable analog (Ser 32 to Ala 32 ) of histone H2B (residues 29-35). 

370655 (DT-3; cGMP-dependent Protein Kinase Ia Inhibitor, Cell-permeable; cGPK Ia Inhibitor, 

Cell-permeable; RQIKIWFQNRRMKWKKLRKKKKKH) 

A highly potent, membrane-permeable peptide that selectively inhibits PKG Ia 

(K i = 25 nM). Inhibitor peptide is fused to the Drosophila Antennapedia homeodomain 

peptide to allow membrane permeability. 

569397 A potent, cell-permeable, and broad spectrum inhibitor of protein kinases. Inhibits 

protein kinase A (IC 50 = 7 nM), CaM kinase (IC 50 = 20 nM), myosin light chain kinase 

(IC 50 = .3 nM), protein kinase C (IC 50 = 700 pM), and protein kinase G (IC 50 = 8.5 nM). 

Also inhibits platelet aggregation induced by collagen or ADP but has no effect on 

thrombin-induced platelet aggregation. Induces apoptosis in human malignant glioma 

cell lines. Arrests normal cells at the G checkpoint. 

44 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

$84 

$327 

mg $84 

set $ 32 

mg $57 

mg $84 

00 mg $ 33 

00 mg $ 28 

50 mg 

00 mg 

50 mg 

00 mg 

00 mg 

250 mg 

$76 

$ 33 

$8 

$ 39 

mg $6 

mg $ 02 

$ 43 

$302

Protein Tyrosine Kinase (PTK) Inhibitors 

Protein tyrosine kinases (PTKs) play a key role in 

the regulation of cell proliferation, differentiation, 

metabolism, migration, and survival. PTKs catalyze the 

transfer of g-phosphoryl groups from ATP to tyrosine 

hydroxyls of proteins. They are classified as receptor 

PTKs and non-receptor PTKs. Receptor PTKs contain 

a single polypeptide chain with a transmembrane 

segment. The extracellular end of this segment contains 

a high affinity ligand-binding domain, while the 

cytoplasmic end comprises the catalytic core and the 

regulatory sequences. The cytosolic end also contains 

tyrosine residues, which become substrates or targets 

for the tyrosine kinase portion of the receptor. PTK 

remains inactive until a ligand binds to the receptor, 

which leads to the dimerization of two ligand-bound 

receptors (exception: the tetrametric insulin receptor). 

Once activated, receptors are able to autophosphorylate 

tyrosine residues outside the catalytic domain. This 

stabilizes the active receptor conformation and creates 

phosphotyrosine-docking sites for proteins that transduce 

signals within the cell. The cytosolic portion of the 

phosphorylated receptor recruits a number of cytosolic 

adapter proteins via interactions between phosphorylated 

tyrosine residues on the receptor and the SH2 domain on 

the adapter molecule. Different proteins have different 

SH2 domains that recognize specific phosphotyrosine 

residues. An SH2-containing protein, Grb2, acts as a 

common adapter protein in a majority of growth factor 

related signaling events. 

Grb2 binding to phosphotyrosine residues changes 

its conformation and allows it to bind to proline-rich 

sequences in the carboxy terminal tail of Sos, a GDP- 

GTP exchange protein. This binding displaces an 

inhibitory domain in Sos and allows the activation of 

Sos, which then translocates to the plasma membrane 

to cause an exchange of GDP for GTP and activates Ras. 

A wide variety of effectors of Ras activation have been 

reported; however, activation of Raf, a cytoplasmic 

protein kinase, is one of the best studied examples. 

Ras binds to the N-terminus of Raf and recruits it to 

the inner surface of the plasma membrane, where it is 

phosphorylated by protein kinase C. Translocation of Raf 

to the membrane positions it in direct proximity to MAP 

kinase kinase (MEK). Raf phosphorylates MEK, which in 

turn phosphorylates MAP kinase (MAPK). In a resting 

cell, MAPK remains inactive because its phosphorylation 

lip excludes ATP access to the binding pocket. However, 


Ligand 

Ligand 

RTK 


P 

Cytoplasm 

MEK binding destabilizes the lip and exposes the buried 

tyrosine residues. Phosphorylation of the exposed 

tyrosine and the nearby threonine residues cause the lip 

to alter its conformation allowing ATP binding. 

Non-receptor tyrosine kinases include members of the 

Src, Tec, JAK, Fes, Abl, FAK, Csk, and Syk families. 

They are located in the cytoplasm as well as in the 

nucleus. They are activated by a large number of stimuli 

including hormones, neurotransmitters, growth factors, 

and cytokines. They exhibit distinct kinase regulation, 

substrate phosphorylation, and function. Deregulation 

of these kinases has also been linked to several human 

diseases. In most cases, their activation also begins 

with the phosphorylation of a tyrosine residue present 

in an activation loop. The best studied enzymes in 

this group include Src kinases. Src is believed to be 

negatively regulated by phosphorylation at Tyr 527 present 

at the C-terminus by Csk and other cellular kinases. 

The enzyme assumes an inactive conformation when 

this phosphotyrosine is bound by the Src SH2 domain 

in an intramolecular fashion. In this structure, the 

Src SH3 domain interacts with a single proline, Pro 250 , 

in the linker region between the SH2 and catalytic 

domain. In contrast to Src, c-Abl kinase activity is 

stimulated by phosphorylation of a catalytic domain 

tyrosine residue, Tyr 412 , either via autophosphorylation 

or transphosphorylation by c-Src. Recent studies have 

indicated that dimerization or oligomerization of c-Abl 

might also be sufficient to activate Abl kinase activity 

in vivo. (continued…) 

RTK 

Nucleus 

P 

SOS 

Grb2 

GDP 

Ras 

Raf1 

MEK 

MAPK 

GTP 

Gene Expression 


Phone 800 628 8470 


45


Protein Tyrosine Kinase (PTK) Inhibitors, continued 

Due to their involvement in various forms of cancers, 

PTKs have become prominent targets for therapeutic 

intervention. Selective receptor and non-receptor PTK 

inhibitors represent a promising class of anti-tumor 

agents. These agents are shown to inhibit multiple 

features of cancer cells, including proliferation, 

survival, invasion, and angiogenesis. 

More online... www.calbiochem.com/inhibitors/PTK 

Protein Tyrosine Kinase (PTK) Inhibitors 

References: 

Tibes, R., et al. 2005. Annu. Rev. Pharmacol. Toxicol. 45, 357. 

Mazitschek, R., Giannis, A. 2004. Curr. Opin. Chem. Biol. 8, 432. 

Martin, G.S. 200 . Nat. Rev. Mol. Cell Biol. 2, 467. 

Ghosh, S., et al. 200 . Curr. Cancer Drug Targets 1, 29. 

Smith, K.M., and Van Etten, R.A. 200 . J. Biol. Chem. 276, 24372. 

Woodside, D.G., et al. 200 . Curr. Biol. 11, 799. 

Sada, K. et al. 200 . J. Biochem. (Tokyo) 130, 77. 

Brasher, B.B., and Van Etten, R.A. 2000. J. Biol. Chem. 275, 3563 . 

Plattner, R., et al. 999. Genes Dev. 13, 2400. 

Manes, G., et al. 999. Gene Ther. Mol. Biol. 4, 4 7. 

Stratowa, C., et al. 999. Anticancer Drug Des. 14, 393. 

Kyriakis, J.M. 999. J. Biol. Chem. 274, 5259. 


A77 726 100128 [N-(4-Trifluoromethylphenyl)-2-cyano-3-hydroxycrotoamide] 

Inhibits the IL-2-induced tyrosine phosphorylation of JAK and JAK3. 

AG 9 658390 {[(4-Methoxybenzylidene)malononitrile; a-Cyano-(4-methoxy)cinnamonitrile]; 

Tyrphostin A1} 

Inactive inhibitor that can be used as a negative control for inhibition of EGFR kinase 

(IC 50 > 250 mM). 

AG 7 658425 [a-Cyano-(3,5-di-t-butyl-4-hydroxy)cinnamonitrile; 3,5-di-t-Butyl-4-hydroxybenzylidenemalononitrile; 

NSC 242557; RG 50872; Tyrphostin A9] 

A selective inhibitor of the platelet-derived growth factor receptor tyrosine kinase 

(IC 50 = 500 nM). 

AG 8 658395 [a-Cyano-(3,4-dihydroxy)cinnamonitrile; RG-50810; Tyrphostin A23] 

An inhibitor of EGFR autophosphorylation (IC 50 = 40 mM) and the GTPase activity of 

transducin (IC 50 = 0 mM). 

AG 30 121760 [a-Cyano-(3,4-dihydroxy)cinnamic Acid; Tyrphostin AG 30] 

A potent protein tyrosine kinase inhibitor that is specific for c-ErbB. 

Inhibits the activation of STAT5 by c-ErbB in primary erythroblasts. 

AG 43 658450 [a-Cyano-(4-hydroxy)dihydrocinnamonitrile; Tyrphostin A63] 

Useful negative control for tyrphostins (IC 50 = 6.5 mM for EGFR tyrosine kinase activity). 

AG 82 658400 [a-Cyano-(3,4,5-trihydroxy)cinnamonitrile; Tyrphostin A25] 

A cell-permeable, competitive inhibitor of substrate binding on protein tyrosine kinases. 

Inhibits EGFR tyrosine kinase (IC 50 = 3 mM) and the GTPase activity of transducin 

(IC 50 = 7 mM). 

AG 99 658430 [a-Cyano-(3,4-dihydroxy)cinnamide; Tyrphostin A46; Tyrphostin B40] 

An inhibitor of EGFR tyrosine kinase (IC 50 = 0 mM) and EGF-dependent cell proliferation. 

AG 2 658440 [2-Amino-4-(4´-hydroxyphenyl)-1,1,3-tricyanobuta-1,3-diene; Tyrphostin A48] 

Inhibits EGFR tyrosine kinase (IC 50 = 25 nM). 

AG 83 658410 [2-Amino-4-(3´,4´,5´-trihydroxyphenyl)-1,1,3-tricyanobuta-1,3-diene; Tyrphostin A51] 

An inhibitor of EGFR tyrosine kinase (IC 50 = 800 nM). 

AG 2 3 658405 [a-Cyano-(3,4-dihydroxy)thiocinnamide; RG-50864; Tyrphostin A47] 

An inhibitor of EGFR tyrosine kinase (IC 50 = 2.4 mM). 

AG 490 658401 [a-Cyano-(3,4-dihydroxy)-N-benzylcinnamide; Tyrphostin B42] 

Potent inhibitor of EGFR kinase autophosphorylation (IC 50 = 00 nM). 

Also acts as a Jak family tyrosine kinase inhibitor. 

N AG 490, m-CF 3 658408 [(alpha-cyano-(3,4-dihydroxy)-N-(m-trifluoromethyl)benzylcinnamide] 

A cell-permeable, m-trifluoromethyl derivative of AG 490 (Cat. No. 65840 ) that 

displays enhanced antiproliferative properties (IC 50 = .7 mM, 2.8 mM, and 6. mM in 

2E8, Baf/3, and Jurkat cells, respectively). Shown to inhibit cytokine-induced JAK kinase 

activities, and promote cell death. Further, causes significant reductions in lymph node 

cellularity in IL7TG mouse model ( mg per animal, intraperitoneal). 

5 mg $ 00 

5 mg $43 

5 mg $52 

5 mg $52 

5 mg $64 

5 mg $66 

5 mg $52 

5 mg $52 

5 mg $52 

5 mg $90 

5 mg $49 

5 mg $38 

0 mg $88 

46 Orders Phone 800 854 34 7 


Fax 800 776 0999 






AG 494 658407 [a-Cyano-(3,4-dihydroxy)-N-phenylcinnamide; Tyrphostin B48] 

Inhibitor of EGFR kinase autophosphorylation (IC 50 = .24 mM) that is slightly less active 

than AG 555 (Cat. No. 658404). 

AG 527 658402 [a-Cyano-(-)-(R)-N-(a-phenethyl)-3,4-dihydroxycinnamide; (-)-(R)-N- 

(a-Methylbenzyl)-3,4-dihydroxybenzylidinecyanoacetamide; Tyrphostin B44(-)] 

An inhibitor of EGFR kinase autophosphorylation (IC 50 = 2.5 mM). Also inhibits the 

phosphorylation of poly-GAT by the EGF receptor (IC 50 = 400 nM). 

AG 537, Bis-Tyrphostin 658418 (Bis-Tyrphostin) 

Competitively inhibits EGFR kinase autophosphorylation (IC 50 = 400 nM). 

AG 538 658403 [a-Cyano-(3,4-dihydroxy)cinnamoyl-(3´,4´-dihydroxyphenyl)ketone; Tyrphostin AG 538] 

A potent, competitive inhibitor of insulin-like growth factor- receptor (IGF- R) 

kinase autophosphorylation (IC 50 = 400 nM). Also inhibits the phosphorylation of PTK 

substrate poly (Glu,Tyr) by IGF- R, IR, EGF-R, and Src (IC 50 = 60 nM, 3 nM, and 2.4 mM 


I-OMe-AG 538 658417 [a-Cyano-(3-methoxy,4-hydroxy,5-iodo)cinnamoyl-(3´,4´-dihydroxyphenyl)ketone; 

Tyrphostin I-OMe-AG 538] 

An analog of AG 538 (Cat. No. 658403) that acts as an inhibitor of IGF- receptor kinase 

both in vitro and in intact cells. Inhibition is competitive with respect to the substrate 

binding site of IGF- receptor kinase. Exhibits enhanced cell-permeability and increased 

resistance to oxidation. 

AG 555 658404 [a-Cyano-(3,4-dihydroxy)-N-(3-phenylpropyl)cinnamide; Tyrphostin B46] 

A potent inhibitor of EGFR kinase autophosphorylation (IC 50 = 700 nM). Exhibits opposite 

potency profiles with AG 527 (Cat. No. 658402) for EGF receptor autophosphorylation 

versus poly-GAT substrate phosphorylation. 

AG 556 658415 [a-Cyano-(3,4-dihydroxy)-N-(4-phenylbutyl)cinnamide; Tyrphostin B56] 

A selective inhibitor of EGFR kinase (IC 50 = 5 mM) over HER -2 kinase autophosphorylation. 

AG 592 658406 {AGL 2592; 2-Cyano-N-(4-{4-[2-cyano-3-(3,4-dihydroxyphenyl)-acryloylamino]cyclohexylmethyl}-cyclohexyl)-3-(3,4-dihydroxyphenyl)-acrylamide} 

A selective, cell-permeable inhibitor of EGFR-tyrosine kinase activity (IC 50 = 20.3 mM). 

Blocks thymidine uptake in HER- 4 cells, and displays anti-proliferative properties. 

AG 825 121765 [4-Hydroxy-3-methoxy-5-(benzothiazolylthiomethyl)benzylidenecyanoacetamide] 

A potent, selective and ATP-competitive inhibitor of HER-2 (neu/erbB-2, IC 50 = 350 nM) 

relative to HER- (IC 50 = 9 mM) autophosphorylation. 

AG 835 658409 [a-Cyano-(+)-(S)-N-(a-phenethyl)-(3,4-dihydroxy)cinnamide; Tyrphostin B50(+)] 

A less active enantiomer of AG 527 (Cat. No. 658402) that inhibits EGFR kinase 

poly-GAT (poly-Glu-Ala-Tyr) substrate phosphorylation (IC 50 = 860 nM). 

AG 879 658460 [a-Cyano-(3,5-di-t-butyl-4-hydroxy)thiocinnamide] 

An inhibitor of nerve growth factor-dependent pp 40 c-trk tyrosine phosphorylation 

(EC 50 = 0 mM). Does not affect the tyrosine phosphorylation of EGFR or PDGFR. 

AG 957 121761 [4-Amino-N-(2,5-dihydroxybenzyl)methyl benzoate; NSC 654705] 

A potent and selective inhibitor of human p2 0 brc-abl (K i = 750 nM) over p 40 bcr-abl 

(K i = 0 mM). 

AG 957, Adamantyl 

Ester 

121762 [4-Amino-N-(2,5-dihydroxybenzyl)adamantyl Benzoate; 4-(2,5-Dihydroxybenzylamino)benzoic 

Acid Adamantan-1-yl Ester] 

A lipophilic, adamantyl ester form of tyrphostin AG 957 (Cat. No. 2 76 ) that displays 

anti-proliferative properties. Shown to be selective and ~3-4 fold more potent than 

AG 957 as a bcr/abl kinase inhibitor, and also exhibits a longer serum half-life in vivo. 

AG 024 121767 (3-Bromo-5-t-butyl-4-hydroxy-benzylidenemalonitrile) 

A specific inhibitor of insulin-like growth factor- (IGF- ) and insulin receptor kinases 

with significantly lower IC 50 values for IGF- than for insulin receptors. 

AG 295 658550 (6,7-Dimethyl-2-phenylquinoxaline) 

A selective inhibitor of PDGFR kinase (IC 50 = 500 nM). Does not affect EGFR 

autophosphorylation. 

5 mg $32 

5 mg $33 

5 mg $69 

5 mg $67 

5 mg $67 

5 mg $33 

5 mg $32 

5 mg $ 78 

2 mg $93 

5 mg $32 

5 mg $90 

5 mg $92 

5 mg $ 84 

mg $67 

5 mg $87 


Phone 800 628 8470 


47




AG 296 658551 (6,7-Dimethoxy-3-phenylquinoxaline) 

More potent than AG 295 (Cat. No. 658550). Inhibits signaling of human PDGF areceptors 

(IC 50 = .0 mM), b-receptors (IC 50 = 800 nM), and the related stem cell factor 

receptor c-kit (80% inhibition at 5 mM). Has no effect on autophosphorylation of the 

vascular endothelial growth factor receptor KDR. 

AG 387 658520 [AG 555, 5-Iodo; a-Cyano-(3,4-dihydroxy)-5-iodo-N-(3-phenylpropyl)cinnamide; 

2-Cyano-3-(3,4-dihydroxy-5-iodo-phenyl)-N-(3-phenylpropyl)acrylamide] 

A 5-iodo analog of AG 555 (Cat. No. 628404) that is more cell-permeable than AG 555. 

Acts as an inhibitor of protein tyrosine kinase and DNA topoisomerase I. 

AG 433 658553 [2-(3,4-Dihydroxyphenyl)-6,7-dimethylquinoxaline, HCl; SU 1433] 

A potent and specific inhibitor of the PDGF b-receptor kinase (IC 50 = 5.0 mM) and of 

KDR/Flk- (IC 50 = 9.3 mM). Also acts as an angiogenesis inhibitor. 

AG 478 658552 [4-(3-Chloroanilino)-6,7-dimethoxyquinazoline] 

A highly potent and specific inhibitor of the EGFR tyrosine kinase (IC 50 = 3 nM). Inhibits 

the kinase activity of the closely-related HER2 (neu/erb-B2) receptor (IC 50 > 00 mM), the 

PDGFR (IC 50 > 00 mM), and p2 0 Bcr-Abl (IC 50 > 50 mM) at much higher concentrations. 

5 mg $97 

5 mg $87 

5 mg $ 

5 mg $ 0 

InSolution AG 478 658548 Supplied as a 0 mM ( mg/3 7 ml) solution of AG 478 (Cat. No. 658552) in DMSO. mg $53 

AGL 2043 121790 {1,2-Dimethyl-6-(2-thienyl)-imidazolo[5,4-g]quinoxaline; Tyrphostin AGL 2043} 

A cell-permeable, potent, selective, ATP-competitive, and reversible inhibitor of type 

III receptor tyrosine kinases, PDGFR (IC 50 = 800 nM in 3T3 cells; 90 nM against purified 

PDGFb-receptor), Flt3, and Kit (IC 50 ~ –3 mM). Weakly inhibits PKA, EGFR, IGF- R, 

VEGFR, and Src kinases (IC 50 > 30 mM). 

AGL 2263 121850 (AG 2263) 

A cell-permeable, potent, substrate-competitive, but not ATP-competitive, inhibitor of 

insulin receptor kinase (IC 50 = 400) and insulin-like growth factor- receptor kinase 

(IC 50 = 430 nM). 

Aminogenistein 155100 (4´-Amino-6-hydroxyflavone) 

Inhibits protein-tyrosine kinase activity of p56 lck (IC 50 = .2 mM). 

Angiogenesis Inhibitor 175580 [(Z,E)-3-(Imidazol-4-ylmethylene)indolin-2-one] 

A cell-permeable, ATP-competitive inhibitor of hEGF-R tyrosine kinase activity (54% 

inhibition at 0 mM). Displays anti-angiogenesis properties (30% inhibition of control at 

0 mM in an in vitro rat aortic ring model) with a potency that is comparable to that of 

SU54 6 (Cat. No. 676487; 22% inhibition of control at 0 mM). Acts as a moderate ATPcompetitive 

inhibitor of hEGF-R tyrosine kinase activity (54% inhibition at 0 mM). 

N Bcr-abl Inhibitor 197221 GNF-2; (3-(6)-(4-Trifluoromethoxy-phenylamino)-pyrimidin-4-yl)-benzamide 

A cell-permeable pyrimidine compound that binds to the c-abl myristoyl binding pocket 

and acts as an allosteric, non-ATP-competitive inhibitor of cellular Bcr-abl activity and 

Bcr-abl-dependent cellular functions. 

BPDQ 203697 {4-[(3-Bromophenyl)amino]-6,7-diaminoquinazoline} 

A highly potent and specific inhibitor of EGFR kinase (IC 50 = 20 pM). 

BPIQ-I 203696 {8-[(3-Bromophenyl)amino]-3-methyl-3H-imidazo[4,5-g]-quinazoline} 

A highly potent and specific inhibitor of EGFR kinase (IC 50 = 25 pM). 

BPIQ-II 203704 {8-[(3-Bromophenyl)amino]-1H-imidazo[4,5-g]-quinazoline} 

One of the most potent and selective inhibitors of EGFR kinase (IC 50 = 8 pM). 

Butein 203987 (2´,4´,3,4-Tetrahydroxychalcone) 

A potent inhibitor of EGFR kinase (IC 50 = 65 mM) and p60 c-src (IC 50 = 65 mM). 

N cFMS Receptor Tyrosine 

Kinase Inhibitor 

344036 A cell-permeable diaminopyrimidine compound that acts as a potent, selective, and 

ATP-competitive inhibitor of cFMS kinase activity (IC 50 = 30 nM) with minimal inhibition 

towards a panel of 26 other kinases (IC 50 > 5 µM). Shown to selectively inhibit cFMSmediated 

cellular functions in vitro as well as CSF- -dependent tumor growth in vivo. 

CL-387,785 233100 {N-[4-[(3-Bromophenyl)amino]-6-quinazolinyl]-2-butynamide; EKI-785} 

An irreversible inhibitor of autophosphorylation of EGFR (IC 50 = 250 - 490 nM). 

Compound 56 234505 {4-[(3-Bromophenyl)amino]-6,7-diethoxyquinazoline} 

One of the most potent inhibitors of EGFR kinase activity (IC 50 = 6 pM). 

mg $ 90 

5 mg $ 52 

mg $ 0 

0 mg $87 

5 mg $ 30 

mg $ 0 

mg $ 0 

mg $ 0 

5 mg $ 44 

mg $82 

mg $98 

500 mg $98 

48 Orders Phone 800 854 34 7 


Fax 800 776 0999 






Cucurbitacin I, Cucumis 

sativus L. 

Curcumin, Curcuma 

longa L. 

238590 (JSI-124) 

A cell-permeable, potent, and highly selective inhibitor of Janus kinase/signal 

transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Suppresses 

STAT3 tyrosine phosphorylation in v-Src-transformed NIH 3T3 cells and human lung 

adenocarcinoma A549 cells (IC 50 = 500 nM). 

239802 [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] 

Inhibits the intrinsic kinase activity of EGFR. Induces apoptosis in both androgendependent 

and androgen-independent prostate cancer cells. 

Daidzein 251600 (4´,7-Dihydroxyisoflavone) 

Inactive analog of Genistein that is also reported to inhibit casein kinase II activity. 

Damnacanthal 251650 (3-Hydroxy-1-methoxyanthraquinone-2-aldehyde) 

Most potent and selective inhibitor of p56 lck tyrosine kinase and p56 lck 

autophosphorylation (IC 50 = 7 nM). Inhibition is competitive with respect to 

peptide binding site and mixed non-competitive with the ATP binding site. 

Daphnetin 268295 (7,8-Dihydroxy-2H-1-benzopyran-2-one; 7,8-Dihydroxycoumarin) 

A broad-spectrum inhibitor of protein kinases. Inhibits EGFR kinase (IC 50 = 7.67 mM), 

PKA (IC 50 = 9.33 mM), and PKC (IC 50 = 25 mM). 

5´-Deoxy-5´methylthioadenosine 

260585 (MeSAdo; MTA) 

Inhibits FGF-2 receptor tyrosine kinase and S49 cell-derived high affinity cAMP 

phosphodiesterase (K i = 62 mM) in vitro. 

DMBI 317200 {(Z)-3-[4-(Dimethylamino)benzylidenyl]indolin-2-one} 

Inhibitor of the tyrosine activity of b-PDGFR (IC 50 = 4 mM in PAC- cells) and 

FGFR (IC 50 = 5 mM). 

EGFR/ErbB-2 Inhibitor 324673 [4557W; 4-(4-Benzyloxyanilino)-6,7-dimethoxyquinazoline] 

A cell-permeable, potent, reversible, and ATP competitive inhibitor of EGFR and c-erbB2 

(IC 50 = 20 nM and 80 nM, respectively). 

Emodin 324694 (6-Methyl-1,3,8-trihydroxyanthraquinone) 

Inhibitor of p56 lck (IC 50 = 8.5 mM). Suppresses HER2/neu tyrosine kinase activity 

in HER2/neu overexpressing cancer cells. 

Erbstatin Analog 324930 (2,5-Dihydroxymethylcinnamate) 

Cell-permeable stable analog of Erbstatin. Competitive inhibitor of EGFR kinase activity 

(IC 50 = 780 nM). Inhibits the activation of v-Abl tyrosine kinase activity. 

Geldanamycin, 

Streptomyces 

hygroscopicus 

345805 Inhibitor of p60 c-src tyrosine kinase activity. Binds Hsp90 and induces degradation of 

tyrosine kinases. 

Genistein 345834 (4´,5,7-Trihydroxyisoflavone) 

A tyrosine kinase inhibitor that also blocks the autophosphorylation of EGFR kinase 

(IC 50 = 2.6 mM). Also acts as an inhibitor of p60 v-src (IC 50 = 25 mM). 

Genistin 345836 (Genistein, 7-O-b-D-Glucopyranoside) 

An inactive analog of the PTK inhibitor Genistein (Cat. No. 345834) and can be used as a 

negative control for Genistein. Reported to reduce bone loss in ovarectomized rats. 

GTP- 4564 371806 (3-Phenyl-1H-benzofuro[3,2-c]pyrazole; 1-Phenyl-3-H-8-oxa-2,3-diazacyclopenta[a]inden) 

A cell-permeable, potent, and specific inhibitor of class III receptor tyrosine kinases 

(IC = 300 nM for c-fms, c-kit, wt-FLT3, and ITD-FLT3; .0 mM for PDGFRb). 

50 

Herbimycin A, 


mg $ 57 

00 mg $35 

25 mg $47 

mg $ 4 

0 mg $50 

50 mg $73 

0 mg $62 

mg $84 

50 mg $69 

mg $44 

00 mg $ 80 

20 mg 

50 mg 

$73 

$ 46 

5 mg $ 06 

5 mg $84 

375670 An inhibitor of p60 c-src (IC 50 = 900 nM). Reversibly binds to the thiol groups of the kinase. 00 mg $ 48 

HNMPA-(AM) 3 397100 (Hydroxy-2-naphthalenylmethylphosphonic Acid Trisacetoxymethyl Ester; Pro-drug II) 

Cell-permeable inhibitor of insulin receptor tyrosine kinase (IC 50 = 00 mM). 

IGF- R Inhibitor, PPP 407247 (Insulin-like Growth Factor-1 Receptor Inhibitor; Picropodophyllin) 

A cell-permeable, potent and specific inhibitor of IGF- R both in vitro 

(IC 50 = nM in cell-free kinase assay; 60 nM and < 50 nM for cell viability and 

receptor autophosphorylation, respectively, in melanoma cell lines) and in vivo 

(complete inhibition of IGF- R-dependent tumor cell growth at 20 mg/kg/ 2 hr s.c. 

in SCID mice) with minimum toxic effect (LD 50 > 500 mg/kg). Exhibits little effect 

towards IR, FGFR, PDGFR and EGFR. 

5 mg $ 3 

mg $95 


Phone 800 628 8470 


49



JAK Inhibitor I 420099 {2-(1,1-Dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinolin-7-one} 

A potent inhibitor of Janus protein tyrosine Kinases (JAKs). Displays potent inhibitory 

activity against JAK (IC 50 = 5 nM for murine JAK ), JAK2 (IC 50 = nM), JAK3 (K i = 

5 nM), and Tyk2 (IC 50 = nM). 

N InSolution JAK 


420097 {2-(1,1-Dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinolin-7-one} 

A 0 mM (500 mg/ 62 ml) solution of JAK Inhibitor I (Cat. No. 420099) in DMSO. 

N JAK2 Inhibitor II 420132 (1,2,3,4,5,6-Hexabromocyclohexane) 

A cell-permeable hexabromocyclohexane compound that acts as a specific and direct 

inhibitor of JAK2 autophosphorylation (maximal inhibition at 50 mM in BSC-40 cells 

overexpressing JAK2). 

JAK3 Inhibitor I 420101 [4-(4´-Hydroxyphenyl)amino-6,7-dimethoxyquinazoline; WHI-P131] 

A specific inhibitor of JAK3 (IC 50 = 78 mM). Does not affect the activity of JAK , JAK2, 

ZAP/Syk, or Src tyrosine kinases. 

JAK3 Inhibitor II 420104 {4-[(3´-Bromo-4´-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline; WHI-P154} 

A potent, cell-permeable inhibitor of JAK3 that is reported to kill glioblastoma cells 

(IC 50 = 8 3 nM). 

JAK3 Inhibitor III 420106 [4-(3´,5´-Dibromo-4-hydroxyphenyl)amino-6,7-dimethoxyquinazoline; WHI-P97] 

A potent and specific inhibitor of JAK3 (IC 50 = mM). 

JAK3 Inhibitor IV 420121 [2-Naphthyl-(N-isopropyl,N-benzyl)-b-aminoethylketone, HCI; ZM 39923] 

A potent and selective ATP-competitive inhibitor of JAK3 (pIC 50 = 7. ). Weakly inhibits 

other tyrosine kinases (pIC 50 = 5.6 for EGF-R; 4.4 for JAK ). In neutral buffer undergoes 

a retro-Michael breakdown (t /2 = 36 min at 25˚C, pH 7.43) to the active analog 2-naphthylvinyl 

ketone (Cat. No. 420 22) [pIC 50 = 6.8 for JAK3; 5.0 for EGF-R; 4.7 for JAK ]. 

JAK3 Inhibitor V 420122 [(2-Naphthylvinyl Ketone); ZM 449829] 

A breakdown product of JAK3 Inhibitor-IV (Cat. No. 420 2 ) with similar inhibitory 

activities (pIC 50 = 6.8 for JAK3; 5.0 for EGF-R; 4.7 for JAK ). Also inhibits STAT-5 

phosphorylation and T-cell proliferation. 

JAK3 Inhibitor VI 420126 A cell-permeable, potent inhibitor of JAK3 (IC 50 = 27 nM). Binds to the enzyme active 

site and prevents IL-2-induced cellular phosphorylation of JAK3 and STAT5. 

JAK3 Inhibitor, Negative 

Control 

420112 (4-Phenylamino-6,7-dimethoxyquinazoline; WHI-P258) 

A useful negative control compound for JAK3 inhibitors. 

Lavendustin A 428150 {5-Amino-[(N-2,5-dihydroxybenzyl)-N´-2-hydroxybenzyl]salicylic Acid; RG14355} 

A potent inhibitor of EGFR kinase (IC 50 = nM) and p60 c-src (IC 50 = 500 nM). 

Lavendustin B 428160 [5-Amino-(N,N´-bis-2-hydroxybenzyl)salicylic Acid] 

A negative control for Lavendustin A (IC 50 = .3 mM for EGFR kinase). 

Lavendustin C 234450 [Compound 5; 5-(N-2´,5´-Dihydroxybenzyl)aminosalicylic Acid] 

Potent inhibitor of p60c-src (IC = 200 nM) and Ca 50 2+ /calmodulin-dependent kinase II 

(IC = 200 nM). 

50 

N Lck Inhibitor 428205 A cell-permeable pyrrolopyrimidine compound that acts as a potent, selective and ATPcompetitive 

inhibitor of Lck (IC at 5 mM of ATP = < nM, 2 nM, 70 nM, .57 mM, and 

50 

.98 mM for Lck Y 64-509 394 , lckcd pY394 , src, kdr, and tie-2, respectively; IC at mM of 

50 

ATP = 6 nM, 66 nM, 26 nM, 420 nM, and 5. 8 mM for Lck Y 64-509 394 , blk, fyn, lyn, and 

csk, respectively). Only minimally affects the activities of other kinases (IC = 3.2 mM, 

50 

> 33 mM, > 50 mM, and > 50 mM for EGFR, PKC, CDC2/B, and ZAP-70, respectively). 

N 


LFM-A 435301 [a-Cyano-b-hydroxy-b-methyl-N-(3-fluorophenyl)propenamide] 

A useful negative control (IC 50 ≥ 454 mM) for LFM-A 3. 

LFM-A 2 435302 {a-Cyano-b-hydroxy-b-methyl-N-[4-(trifluoromethoxy)phenyl]propenamide} 

A potent and specific inhibitor of EGFR kinase (IC 50 = .7 mM). 

LFM-A 3 435300 [a-Cyano-b-hydroxy-b-methyl-N-(2,5-dibromophenyl)propenamide] 

A potent and specific inhibitor of Bruton’s tyrosine kinase (BTK; IC 50 = 7.2 mM for human 

BTK in vitro and IC 50 = 2.5 mM for recombinant BTK). 

Met Kinase Inhibitor 448101 (3Z)-N-(3-Chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1Hpyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; 

SU11274 

A cell-permeable pyrrole indolinone compound that acts as a potent, reversible, and 

ATP-competitive inhibitor of Met kinase activity (IC = 20 nM). 

50 

500 mg $83 

500 mg $83 

25 mg $88 

5 mg $ 8 

5 mg $ 50 

mg $ 27 

0 mg $ 90 

0 mg $ 68 

5 mg $ 5 

50 Orders Phone 800 854 34 7 


Fax 800 776 0999 


500 mg 

mg 

500 mg 

mg 

500 mg 

mg 

$76 

$ 27 

mg $ 7 

mg $ 7 

mg $62 

mg $82 

$44 

$75 

$ 42 

$230 

5 mg $98 

mg $85





Oxindole I 499600 [3-(1H-Pyrrol-2-ylmethylene)-1,3-dihydroindol-2-one] 

A potent and specific inhibitor of VEGFR kinase Flk- (IC 50 = 390 nM). 

PD 53035 234490 {AG 1517; 4-[(3-Bromophenyl)amino]-6,7-dimethoxyquinazoline; Compound 32; SU 5271} 

An extremely potent and specific inhibitor of EGFR kinase activity (IC 50 = 25 pM). 

0 mg $64 

mg $85 

N InSolution PD 53035 234491 A 0 mM (500 mg/ 39 ml) solution of PD 53035 (Cat. No. 234490) in DMSO. 500 mg $85 

PD 56273 513032 {6-Amino-4-[(3-bromophenyl)amino]-7-(methylamino)quinazoline} 

A potent inhibitor of EGFR kinase activity (IC 50 = 690 pM). 

PD 58780 513035 {4-[(3-Bromophenyl)amino]-6-(methylamino)-pyrido[3,4-d]pyridimine} 

A potent inhibitor of the EGFR tyrosine kinase activity (80 pM). Also inhibits heregulinstimulated 

autophosphorylation in SK-BR-3 (IC 50 = 49 nM) and MDA-MB-453 

(IC 50 = 52 nM) breast carcinomas. 

PD 68393 513033 {4-[(3-Bromophenyl)amino]-6-acrylamidoquinazoline} 

A potent, cell-permeable, irreversible, and selective inhibitor of EGFR kinase activity 

(IC 50 = 700 pM). 

PD 74265 513040 {4-[(3-Bromophenyl)amino]-6-propionylamidoquinazoline} 

A potent, cell-permeable, reversible, and selective inhibitor of EGFR kinase activity 

(IC 50 = 450 pM). 

PDGF Receptor Tyrosine 

Kinase Inhibitor I 


Kinase Inhibitor II 


Kinase Inhibitor III 

521230 [D-64406; (5-Hydroxy-1H-2-indolyl)(1H-2-indolyl)-methanone] 

A cell-permeable bis( H-2-indolyl)- -methanone compound that acts as a highly 

selective and ATP-competitive inhibitor of PDGFR kinase (IC 50 = 200 nM in Swiss 3T3 

cells for PDGFR; 90 nM in vitro and 200 nM in PAE cells for PDGFb-R; mM for 

PDGFa-R). Also reported to inhibit Fms-like tyrosine kinase 3 (Flt3) activity 

(IC 50 = 300 nM for hPDGFb-R-mFlt3 and 00 nM in EOL- cells). 

521231 {(5-Butanoate-1H-2-indolyl)(1H-2-indolyl)-methanone; D-65476; 

[2-(1H-2-Indolylcarbonyl)-1H-5-indolyl]butanoate} 

Prodrug form of Platelet Derived Growth Factor Receptor Tyrosine Kinase Inhibitor I 

(Cat. No. 52 230) that acts as a highly selective, cell-permeable, ATP-competitive inhibitor 

of PDGFR kinase (IC 50 = . mM, Swiss 3T3 cells). A potent inhibitor of Fms-like tyrosine 

kinase 3 (Flt3) activity (IC 50 = 6.2 mM for PDGFRb-mFlt3 and 50 nM in EOL- cells). 

521232 [4-(6,7-Dimethoxy-4-quinazolinyl)-N-(4-phenoxyphenyl)-1-piperazinecarboxamide] 

A cell-permeable, potent, selective, ATP-competitive inhibitor of PDGF receptor family 

of tyrosine kinases (IC 50 = 50 nM for a-PDGFR; 80 nM for b-PDGFR; 50 nM for c-Kit; 

230 nM for Flt3). 


Inhibitor of p72 Syk , a non-receptor tyrosine kinase (IC 50 = 0 mM). 

PP Analog 529579 {4-Amino-1-tert-butyl-3-(1´-naphthyl)pyrazolo[3,4-d]pyrimidine} 

A potent, cell-permeable, and selective inhibitor of Src-family tyrosine kinases. Displays 

high selectivity for 338G v-Src (IC 50 = .5 nM) with respect to the wild-type v-Src 

(IC 50 = .0 mM). Also inhibits wild-type Fyn (IC 50 = 600 nM). Not available for sale in the 

United States. 

N PP Analog II, NM- 

PP 

529581 {4-Amino-1-tert-butyl-3-(1´-naphthylmethyl)pyrazolo[3,4-d]pyrimidine; Mutant Kinases 

Inhibitor II; NM} 

A cell-permeable PP analog (Cat. No. 529479) that acts as a potent and selective 

ATP-competitive inhibitor of mutant kinases over wild-type (IC = 3.2 nM for T339G, 

50 

c-Fyn-as vs. .0 mM for c-Fyn; 4.3 nM for I338G, v-src-as vs. 28 mM for v-src; 5 nM 

for F80G, CDK2-as vs. 29 mM for CDK2; 8 nM for F89G, CAMK IIa-as vs. 24 mM for 

CaMKII; 20 nM for T3 5A, c-Abl-as2 vs. 3.4 mM for c-Abl). Shown to activate mutants 

of Ire , a transmembrane kinase. 

PP2 529573 {AG 1879; 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine} 

A potent and selective inhibitor of the Src family of tyrosine kinases. Inhibits p56 lck 

(IC 50 = 4 nM), p59 fynT (IC 50 = 5 nM), and Hck (IC 50 = 5 nM). 

mg $ 04 

500 mg $ 07 

mg $ 04 

mg $93 

mg $ 37 

mg $ 57 

mg $ 05 

mg $4 

mg — 

mg $82 

mg $92 

InSolution PP2 529576 A 0 mM ( mg/33 ml) solution of PP2 (Cat. No. 529573) in DMSO. mg $97 

PP3 529574 (4-Amino-7-phenylpyrazol[3,4-d]pyrimidine) 

A negative control compound for PP2. Shown to inhibit EGFR kinase (IC 50 = 2.7 mM). 

mg $57 


Phone 800 628 8470 


5




Radicicol, 

Diheterospora 

chlamydosporia 

553400 Inhibitor of p60 v-src kinase activity (IC 50 = 8.2 mM). Also inhibits tyrosine 

phosphorylation of p53/56 lyn in LPS-stimulated macrophages. 

RG- 3022 554725 [a-(3´-Pyridyl)-(3,4-dimethoxy)cinnamonitrile] 

A selective inhibitor of EGFR kinase activity. Inhibits epidermal growth factor- 

stimulated HER 4 cell proliferation (IC 50 = mM) and tumor growth in vivo. 

Src Kinase Inhibitor I 567805 [4-(4´-Phenoxyanilino)-6,7-dimethoxyquinazoline] 

A potent, selective, dual site, competitive inhibitor of Src tyrosine kinase (IC 50 = 44 nM 

and 88 nM for Src and Lck, respectively). Shown to simultaneously interact with both 

the ATP- and peptide-binding sites. Inhibits VEGFR2 and c-fms tyrosine kinases only at 

higher concentrations (IC 50 = 320 nM and 30 mM, respectively). 

Src Kinase Inhibitor II 567806 A potent, selective, and ATP-competitive inhibitor of Src family tyrosine kinases 

(IC 50 = .2 mM for human recombinant Csk). 

ST638 567790 [a-Cyano-(3-ethoxy-4-hydroxy-5-phenylthiomethyl)cinnamide] 

Protein tyrosine kinase inhibitor (IC 50 = 370 nM) that also inhibits HGF-induced MAP 

kinase activation in hepatocytes. 

SU 498 572888 {(E)-3-(3,5-Diisopropyl-4-hydroxyphenyl)-2-[(3-phenyl-n-propyl) 

amino-carbonyl]acrylonitrile} 

A potent and selective inhibitor of Flk- kinase (IC 50 = 700 nM), a vascular endothelial 

growth factor (VEGF) receptor kinase. Also reduces the expression of ets-1, a 

transcription factor stimulated by VEGF. Has only a weak inhibitory effect on PDGFreceptor 

(IC 50 > 50 mM), EGF-receptor (IC 50 > 00 mM), and HER2 (IC 50 > 00 mM). 

SU4984 572625 {3[4-(1-Formylpiperazin-4-yl)benzylidenyl]-2-indolinone} 

Inhibitor of FGFR tyrosine kinase activity (IC 50 = 0–20 mM in the presence of mM 

ATP). Also inhibits aFGF-induced phosphorylation of ERK and ERK2 and tyrosine 

phosphorylation of PDGF and insulin receptors. Not available for sale in the United 

States. 

SU5402 572630 {3-[3-(2-Carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone} 

Inhibits the tyrosine kinase activity of fibroblast growth factor receptor (FGFR ); 

(IC 50 = 0–20 mM in the presence of mM ATP). Also inhibits aFGF-induced tyrosine 

phosphorylation of ERK and ERK2 (IC 50 = 0–20 mM). In contrast to SU4984 

(Cat. No. 572625), SU5402 is only a weak inhibitor of tyrosine phosphorylation of the 

PDGF receptor and does not inhibit phosphorylation of the insulin receptor. Does not 

inhibit the kinase activity of the EGF receptor. Not available for sale in the United States. 

SU56 4 572632 {5-Chloro-3-[(3,5-dimethylpyrrol-2-yl)methylene]-2-indolinone} 

Potent inhibitor of VEGFR kinase, Flk- (IC 50 = .2 mM), and PDGFR kinase 

(IC 50 = 2.9 mM). Not available for sale in the United States. 

500 mg $75 

5 mg $ 03 

mg $ 03 

5 mg $ 52 

5 mg $ 28 

5 mg $ 23 

mg — 

500 mg — 

mg — 

SU6656 572635 A potent Src family kinase inhibitor. Inhibits Src (IC = 280 nM) and closely related 

50 

kinases Fyn (IC = 70 nM) and Yes (IC = 20 nM). Also inhibits Lyn (IC = 30 nM), 

50 50 50 

but only weakly inhibits Lck (IC = 688 mM) and PDGFR (IC > 0 mM). 

50 50 

mg $ 27 

N InSolution SU6656 572636 A 0 mM (500 mg/ 35 ml) solution of SU6656 (Cat. No. 572635) in DMSO. 500 mg $84 

N SU 652 572660 {5-[(Z)-(5-Chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N- 

[2-(diethylamino)ethyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide} 

A cell-permeable, pyrrole-indolinone compound that acts as a potent and ATPcompetitive 

tyrosine kinase receptor and angiogenic inhibitor that exhibits greater 

selectivity for PDGFRb (IC 50 = 3 nM), VEGFR2 (IC 50 = 27 nM), FGFR (IC 50 = 70 nM), and 

Kit family members (IC 50 = ~ 0–500 nM) over EGFR (IC 50 = > 20 mM). 

Syk Inhibitor 574711 [3-(1-Methyl-1H-indol-3-yl-methylene)-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; 

Spleen Tyrosine Kinase Inhibitor] 

A cell-permeable, potent inhibitor of Syk (IC 50 = 4 nM). 

N Syk Inhibitor II 574712 2-(2-Aminoethylamino)-4-(3-trifluoromethylanilino)-pyrimidine-5-carboxamide, 


A cell-permeable pyrimidine-carboxamide compound that acts as a potent, selective 

and ATP-competitive inhibitor of Syk (IC 50 = 4 nM), and blocks 5-HT release from 

stimulated RBL-2H3 cells (IC 50 = 460 nM). 

500 mg $ 42 

5 mg $ 05 

mg $75 

52 Orders Phone 800 854 34 7 


Fax 800 776 0999 






TGF-b RI Kinase 


N TGF-b RI Kinase 


616451 {ALK5 Inhibitor I; [3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole; TbR-I Inhibitor; 

Transforming Growth Factor-b Type I Receptor Kinase Inhibitor} 

A cell-permeable, potent, selective, ATP-competitive inhibitor of TGF-b type I receptor 

tyrosine kinase (IC 50 = 5 nM). Displays ~ 5-fold greater selectivity over p38a MAP 

kinase (IC 50 = 740 nM). 

616452 [ALK5 Inhibitor II; 2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine; 

Transforming Growth Factor-b Type I Receptor Kinase Inhibitor II] 

A cell-permeable naphthyridinyl pyrazolo compound that acts as a potent, selective, 

and ATP-competitive inhibitor of TGF-b type I receptor (ALK5; IC 50 = 23 nM, 4 nM, and 

8 nM for ALK5 binding, ALK5 auto-phosphorylation and TGF-b cellular assay in HepG2 

cells, respectively). Minimally affects a panel of nine closely related kinases including 

p38 MAPK at IC 50 > 6 mM. 

2´-Thioadenosine 589400 (PD 157432) 

A potent, selective, and irreversible inhibitor of the ErbB subfamily of protein tyrosine 

kinases. Inactivates ErbB by modifying Cys 797 at the active site. Also inhibits ErbB2 

(IC 50 = 45 mM). 

(-)-Terreic Acid, 

Synthetic 

581810 {(1R,6S)-3-Hydroxy-4-methyl-7-oxabicyclo[4.1.0]hept-3-ene-2,5-dione} 

A cell-permeable, selective inhibitor of Bruton’s tyrosine kinase (BTK; IC 50 = 0 mM 

and 3 mM for the basal and activation levels), both in vitro and in vivo. 

N TrkA Inhibitor 648450 An oxindole compound that acts as a potent and highly selective inhibitor of TrkA 

(IC 50 = 6 nM), presumably by targeting the ATP-binding pocket of the kinase. Shown to 

exhibit ≥ 00-fold selectivity over c-fms, Cdk , Cdk2, Itk, JNK-3, p38, PDHK4, c-Raf , 

Src, UL 3, and VEGFR2. 

TX- 23 655200 [2-((3,5-di-tert-Butyl-4-hydroxyphenyl)-methylene)-4-cyclopentene-1,3-dione] 

A cell-permeable inhibitor for Src, eEF2 kinase, and PKA (IC 50 = 2.2, 3.2, and 9.6 mM, 

respectively). Inhibits EGFR kinase and PKC only at much higher concentrations 

(IC 50 = 320 mM). 

N Tyrene CR4 655230 A cell-permeable hydroxystryrylacrylonitrile compound that potently inhibits the kinase 

activities of JAK2 and Bcr-Abl (IC 50 ~ 00–600 nM and 500–700 nM, respectively), and 

displays selectivity over other related kinases, namely, Btk, Lck, Lyn, Src, Syk, and 

ZAP-70 (IC 50 > 5 mM). 

Tyrosine-Specific 

Protein Kinase Inhibitor 

VEGF Receptor Tyrosine 

Kinase Inhibitor 

N VEGF Receptor Tyrosine 


VEGF Receptor 2 Kinase 






N InSolution VEGF 

Receptor 2 Kinase 


657015 (p60 v-src 137-157 Inhibitor Peptide; VAPSDSIQAEEWYFGKITRRE) 

Inhibits p60 v-src (IC 50 = 7.5 mM) and epidermal growth factor receptor kinase. 

676475 {4-[(4´-Chloro-2´-fluoro)phenylamino]-6,7-dimethoxyquinazoline} 

A potent inhibitor of vascular endothelial growth factor (VEGF) receptor (Flt and KDR) 

tyrosine kinase activity (IC 50 = 2.0 mM and 00 nM for Flt and KDR, respectively). 

676481 {N-(4-Chlorophenyl)-2-[(pyridin-4-ylmethyl)amino]benzamide} 

Shown to potently inhibit the kinase activities of KDR, Flt- , and c-Kit (IC 50 = 20 nM, 

80 nM, and 240 nM, respectively), and minimally inhibit c-Src and EGF-R activities 

(IC 50 = 7.0 mM and 7.3 mM). Further, inactive towards the inhibition of CDK- , c-Met, 

IGF- R, and PKA (IC 50 > 0 mM). 

676480 {(Z)-3-[(2,4-Dimethyl-3-(ethoxycarbonyl)pyrrol-5-yl)methylidenyl]indolin-2-one} 

A highly selective, cell-permeable indolin-2-one class of receptor tyrosine kinase 

inhibitor (IC 50 = 70 nM) for murine vascular endothelial growth factor receptor 2 (VEGF- 

R2; KDR/Flk- ). The inhibition is suggested to be competitive with respect to ATP. 

676485 [(Z)-5-Bromo-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylene)-1,3-dihydroindol-2-one] 

A cell-permeable receptor tyrosine kinase (RTK) inhibitor [IC 50 = 70 nM for VEGF-R2 

(KDR/Flk- ), 920 nM for PDGF-Rb, 4.92 mM for p60 c-src , and 3.3 mM for FGF-R ]. 

The inhibition is suggested to be competitive with respect to ATP. 

676487 {3-[(2,4-Dimethylpyrrol-5-yl)methylidene]-indolin-2-one; SU5416} 

A cell-permeable, selective, ATP-competitive inhibitor of VEGF-R (KDR/Flk- ) and 

PDGFR kinases (IC 50 = mM and 20 mM, respectively in NIH-3T3 cells overexpressing 

Flk- ; K m = 530 nM for ATP). 

676498 A 0 mM (500 mg/2 0 ml) solution of VEGF Receptor 2 Kinase Inhibitor III 

(Cat. No. 676487) in DMSO. 

5 mg $ 05 

mg $98 

2 mg $ 29 

2 mg $ 03 

mg $ 00 

0 mg $90 

5 mg $82 

500 mg $204 

mg $85 

5 mg $ 29 

mg $99 

mg $99 

mg $ 8 

500 mg $73 


Phone 800 628 8470 


53





Inhibitor IV 

N VEGF Receptor 2 Kinase 

Inhibitor V, ZM32388 


Inhibitor, MAZ5 

N VEGF Receptor Tyrosine 


676489 {KDR/Flk-1 Kinase Inhibitor IV; 3-(3-Thienyl)-6-(4-methoxyphenyl)pyrazolo 

[1,5-a]pyrimidine} 

A potent, ATP-competitive inhibitor of the kinase activity VEGF receptor-2 (VEGFR-2; 

KDR/Flk- ) (IC 50 = 9 nM). Displays ~2-fold greater selectivity for VEGFR-2 compared to 

platelet derived growth factor receptor b (PDGFRb) and 0-fold selectivity compared to 

VEGFR- (Flt- ) and VEGFR-3 (Flt-4). 

676497 [5-((7-(Benzyloxy)quinazolin-4-yl)amino)-4-fluoro-2-methylphenol; KDR/Flk-1 Inhibitor V] 

A cell-permeable anilinoquinazolino compound that acts as a potent and reversible 

inhibitor of VEGFR-2 (KDR/Flk- ; IC 50 < 2 nM) with excellent selectivity over VEGFR- 

and many other receptor tyrosine kinases (IC 50 > 50 mM for VEGFR- , EGFR, ErbB2, 

FGFR , HGFR, and PDGFRb). 

676492 [3-(4-Dimethylamino-naphthalen-1-ylmethylene)-1,3-dihydro-indol-2-one; MAZ51] 

A cell-permeable, ATP-competitive inhibitor of VEGFR kinase. At low concentrations 

(5 mM), reported to specifically block VEGF-C and VEGF-D-induced phosphorylation 

of VEGFR-3, but not VEGFR-2, in PAE cells. Reported to partially block VEGFR-2 

phosphorylation only at higher concentrations (50 mM). 

676481 {N-(4-Chlorophenyl)-2-[(pyridin-4-ylmethyl)amino]benzamide} 

Shown to potently inhibit the kinase activities of KDR, Flt- and c-Kit (IC 50 = 20 nM, 

80 nM, and 240 nM, respectively), and minimally inhibit c-Src and EGF-R activities 

(IC 50 = 7.0 mM and 7.3 mM). Further, inactive towards the inhibition of CDK- , c-Met, 

IGF- R, and PKA (IC 50 > 0 mM). 

Src Family Protein Tyrosine Kinase Inhibitor Set 

A set of 4 vials. Each set contains 20 mg of Genistein (Cat. No. 345834), 

00 mg of Herbimycin A, Streptomyces sp. (Cat. No. 375670), and mg 

each of PP2 (Cat. No. 529573) and PP3 (Cat. No. 529574). 

Cat. No. 567816 1 set $284 

Tyrosine Kinase Inhibitor Set II 

mg $73 

500 mg $95 

0 mg $93 

5 mg $ 29 

A set of 5 vials. Each set contains 20 mg of Genistein (Cat. No. 345834), 

mg of PP2 (Cat. No. 529573), 5 mg of AG 490 (Cat. No. 65840 ), 5 mg 

of AG 296 (Cat. No. 65855 ), and 5 mg of AG 478 (Cat. No. 658552). 

Cat. No. 657021 1 set $273 

54 Orders Phone 800 854 34 7 


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Raf Kinase Inhibitors 

Raf kinases are a group of serine/threonine kinases 

that include A-Raf, B-Raf, and c-Raf1. A-Raf is 

abundant in urogenital tissues, B-Raf is predominantly 

expressed in neural tissue, and c-Raf1 is ubiquitous 

in its distribution. Raf kinases play an important 

role as extracellular signal-regulating kinases in cell 

differentiation, proliferation, and apoptosis. The three 

Raf proteins share a common structure consisting of an 

N-terminal regulatory domain and a C-terminal kinase 

domain. Each Raf has three conserved regions, CR1, 

CR2, and CR3. In the regulatory domain, CR1 contains 

a Ras-binding domain and a cysteine-rich domain, CR2 

is a serine/threonine-rich domain, and CR3 contains 

the kinase domain and is essential for Raf activity. 

The removal of the regulatory domain generates an 

oncogenic kinase. 

All three Raf proteins also share common mechanisms 

of activation and downstream effectors. They work at 

the entry point of the mitogen-activated protein kinase/ 

extracellular-signal-regulated kinase (MAPK/ERK) 

pathway, a signaling module that connects cell-surface 

receptors and Ras proteins to nuclear transcription 

factors. They serve as downstream effectors of Ras 

signaling; however, the interaction between Ras and Raf 

alone is not sufficient for full activation of Raf kinases. 

Raf Kinase Inhibitors 



Additional proteins and enzymes are required for full 

activation. 14-3-3 proteins are known to bind directly 

to Raf and their binding to Ser 621 of Raf-1 is essential 

to keep Raf in an inactive, but activation-competent 

confirmation. PKA is reported to phosphorylate Ser 43 

and Ser 621 and prevent the activation of Raf1. Inhibition 

of PKA has been linked to the growth factor-induced 

activation of c-Raf1. Ser 728 in the 14-3-3 binding 

region in B-Raf is also known to be a target for PKA 

phosphorylation. 

Abnormal activation of Raf signaling pathway is 

common in several type of cancers. Hence, there is 

a significant interest in the development of specific 

inhibitors that may reverse the progression of these 

tumors. These inhibitors may block the expression of Raf 

protein, block its interaction with Ras, or block its kinase 

activity. 

References: 

OíNeill, E., and Kolch, W. 2004. Br. J. Cancer. 90, 283. 

Bollag, G., et al. 2003. Curr. Opin. Investig. Drugs 4, 436. 

Chong, H., et al. 2003. Cell Signal. 15, 463. 

Kolch, W., et al. 2002. Expert Rev. Mol. Med. 25, . 


Raf Kinase Inhibitor I 553008 {5-Iodo-3-[(3,5-dibromo-4-hydroxyphenyl)methylene]-2-indolinone} 

A potent c-Raf kinase inhibitor (IC 50 = 9 nM). Shows ≥ 00-fold selectivity for 

Raf kinase versus Cdk , Cdk2, c-src, ERK2, MEK, p38, Tie2, VEGFR2, and c-fms. 

N InSolution Raf 

Kinase Inhibitor I 

More online... www.calbiochem.com/inhibitors/Raf 

mg $99 

553003 A 0 mM (500 mg/96 ml) solution of Raf Inhibitor I (Cat. No. 553008) in DMSO. 500 mg $63 

ZM 336372 692000 {N-[5-(3-Dimethylaminobenzamido)-2-methylphenyl]-4-hydroxybenzamide} 

A potent, specific, and competitive inhibitor of c-Raf (IC 50 = 70 nM). Inhibits c-Raf with 

ten-fold greater potency compared to B-Raf. Has no significant effect on many other 

protein kinases tested (even at 50 mM) with the exception of SAPK2a/p38a 

(IC 50 = 2 mM) and SAPK2b/p38b2 (IC 50 = 2 mM). 

mg $ 27 


Phone 800 628 8470 


55


Rho Kinase (ROCK) Inhibitors 

Rho kinase (ROCK), a serine/threonine kinase, serves 

as a target protein for small GTP-binding protein Rho. 

It serves as an important mediator of numerous cellular 

functions, including focal adhesions, motility, smooth 

muscle contraction, and cytokinesis. In smooth muscle, 

ROCK plays an important role in Ca 2+ sensitization and 

the control of vascular tone. It modulates the level of 

phosphorylation of the myosin II light chain of myosin 

II, mainly through inhibition of myosin phosphatase, 

and contributes to agonist-induced Ca 2+ sensitization in 

smooth muscle contraction. 

Rho kinase is found in two forms, ROCK 1 (ROCKb; p160- 

ROCK) and ROCK 2 (ROCKa). Both ROCK 1 and ROCK 2 

contain an amino-terminal catalytic kinase domain, a 

central coiled-coil domain of about 600 amino acids, and 

a carboxyl-terminal pleckstrin homology (PH) domain 

Rho Kinase (ROCK) Inhibitors 

that is split by a cysteine-rich region. Rho/GTP interacts 

with the C-terminal portion of the central coiled-coil 

domain and activates the kinase activity of ROCK. Since 

the ROCK-mediated pathway plays important roles in 

vascular smooth muscle contraction, cell adhesion, 

and cell motility, it has gained importance in the 

pathogenesis of atherosclerosis. ROCK inhibitors are 

shown to suppress coronary artery spasms. A long-term 

inhibition of ROCK is reported to block the development 

of coronary arteriosclerotic lesions. 

References: 

Hu, E., and Lee, D. 2003. Curr. Opin. Investig. Drugs. 4, 065. 

Fukata, Y., et al. 200 . Trends Pharmacol. Sci. 22, 32. 

Eto, Y., et al. 2000. Am. J. Physiol. Heart Circ. Physiol. 278, H 744. 

Fujisawa, K., et al. 996. J. Biol. Chem. 271, 23022. 


HA 077, 



A cell-permeable Ca 2+ antagonist that inhibits Rho-associated kinase, PKA 

(IC 50 = .6 mM), PKG (IC 50 = .6 mM), and MLCK (IC 50 = 3.6 mM). 

N Hydroxyfasudil 390602 [1-(1-Hydroxy-5-isoquinolinesulfonyl)homopiperazine, HCl; HA1100] 

Supplied as a 0 mM (2 mg/582 ml) solution in H 2 O. A cell-permeable hydroxylated 

metabolite of HA 077 (Fasudil; Cat. No. 37 970) that displays anti-anginal properties. 

Acts as an ATP-competitive and a reversible inhibitor of Rho-kinase (IC 50 ~0.9– .8 mM) 

with ~ 00-fold greater selectivity over MLCK and PKC. Reported to inhibit the induced 

Ca 2+ -sensitization of contraction both in vitro and in vivo. 

Rho-Kinase Inhibitor 555550 {H-1152; H-1152P; (S)-(+)-2-Methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl] 

homopiperazine, 2HCl; ROCK Inhibitor} 

N InSolution Rho Kinase 


A cell-permeable, highly specific, potent, and ATP-competitive inhibitor of G-protein 

Rho-associated kinase (ROCK; K i = .6 nM). 

mg $84 

2 mg $88 

mg $ 65 

555552 A 0 mM (500 mg/ 28 ml) solution of Rho Kinase Inhibitor (Cat. No. 555550) in H 2 O. 500 mg $90 

Rho-Kinase Inhibitor II 555551 [N-(4-Pyridyl)-N´-(2,4,6-trichlorophenyl)urea] 

A potent, selective, and ATP-competitive inhibitor of Rho-associated protein kinase 

(ROCK; IC 50 = 200 nM). 

N Rho-Kinase Inhibitor III, 

Rockout 

More online... www.calbiochem.com/inhibitors/ROCK 

555553 [3-(4-Pyridyl)-1H-indole] 

A cell-permeable indolopyridine compound that acts as a selective, ATP-competitive 

inhibitor of Rho kinase activity with an IC 50 of 25 mM. Does not inhibit the activation of 

Rho kinase nor does it affect the in vitro activities of MLCK, PKC a , and SAPK2a/p38a. 

Shown to be 5-fold less potent than Y-27632 (Cat. No. 688000; IC 50 ~5 mM), and display 

a similar specificity profile as H-89 (Cat. No. 37 963). 

N Rho Kinase Inhibitor IV 555554 H-1152, Glycyl 

(S)-(+)-2-Methyl-4-glycyl-1-(4-methylisoquinolinyl-5-sulfonyl)homopiperazine, 2HCl 

A glycyl analog of Rho-Kinase Inhibitor (Cat. No. 555550) that inhibits ROCK with an 

improved selectivity (IC 50 = .8 nM, > 0 mM, > 0 mM, 3.26 mM, 2.35 mM, and 2.57 mM 

for ROCKII, PKA, PKC, PKG, Aurora A, and CaMKII, respectively). 

5 mg $ 32 

0 mg $88 

mg $ 55 

56 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Rho Kinase (ROCK) Inhibitors, continued 




Y-27632 688000 [(R)-(+)-trans-N-(4-Pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide, 2HCl; 

ROCK Inhibitor] 

A highly potent, ATP-competitive, cell-permeable, selective inhibitor of Rho- 

associated protein kinase (K i = 40 nM for p 60 ROCK ). Also inhibits ROCK-II with 

almost equal potency. 

InSolution Y-27632 688001 A 5 mM (500 mg/296 ml) solution of Y-27632 (Cat. No. 688000) in H 2 O. 500 mg $75 

Sphingosine Kinase Inhibitors 


Sphingosine Kinase 



N,N-Dimethyl- 

TGF-b Receptor I Kinase Inhibitors 






567731 [2-(p-Hydroxyanilino)-4-(p-chlorophenyl) thiazole; SK Inhibitor] 

A cell-permeable disubstituted thiazole compound that acts as a potent, non-ATPcompetitive, 

and highly specific inhibitor of sphingosine kinase (IC 50 = 500 nM for 

GST-hSK). Does not affect the kinase activity of hERK2, hPI3K, or PKC a even at 

concentrations as high as 60 mM. 

616451 {ALK5 Inhibitor I; [3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole; TbR-I Inhibitor; 

Transforming Growth Factor-b Type I Receptor Kinase Inhibitor} 

A cell-permeable, potent, selective, ATP-competitive inhibitor of TGF-b RI tyrosine kinase 

(IC 50 = 5 nM). Displays ~ 5-fold greater selectivity over p38a MAP kinase (IC 50 = 740nM). 

616452 [ALK5 Inhibitor II; 2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine; 

Transforming Growth Factor-b Type I Receptor Kinase Inhibitor II] 

A cell-permeable, potent, selective and ATP-competitive inhibitor of TGF-b type I receptor 

(ALK5; IC 50 = 23 nM, 4 nM, and 8 nM for ALK5 binding, ALK5 auto-phosphorylation and 

TGF-b cellular assay in HepG2 cells, respectively). Minimally affects a panel of 9 closely 

related kinases including p38 MAPK at IC 50 > 6 mM. 

mg 

5 mg 

$ 27 

$496 

0 mg $84 

310500 An inhibitor of sphingosine kinase. 5 mg $8 

5 mg $ 05 

mg $98 


Phone 800 628 8470 


57


Protein Phosphatase Inhibitors 

Phosphorylation and dephosphorylation of structural 

and regulatory proteins are major intracellular control 

mechanisms in eukaryotes. Protein kinases transfer a 

phosphate from ATP to a specific protein, typically at 

serine, threonine, or tyrosine residues. Phosphatases 

remove the phosphoryl group and restore the protein 

to its original dephosphorylated state. Hence, the 

phosphorylation-dephosphorylation cycle can be 

regarded as a molecular "on-off" switch. 

Protein phosphatases (PPs) have been classified into 

three distinct categories: serine/threonine (Ser/Thr)specific, 

tyrosine-specific, and dual-specificity 

phosphatases. Based on biochemical parameters, 

substrate specificity, and sensitivity to various 

inhibitors, Ser/Thr protein phosphatases are divided 

into two major classes. Type I phosphatases, which 

include PP1, can be inhibited by two heat-stable 

proteins known as Inhibitor-1 (I-1) and Inhibitor-2 (I- 

2). They preferentially dephosphorylate the b-subunit 

of phosphorylase kinase. Type II phosphatases are 

subdivided into spontaneously active (PP2A), Ca 2+ - 

dependent (PP2B), and Mg 2+ -dependent (PP2C) classes 

of phosphatases. They are insensitive to heat-stable 

inhibitors and preferentially dephosphorylate the asubunit 

of phosphorylase kinase. 

Protein tyrosine phosphatases (PTPs) are relatively 

recent additions to the phosphatase family. They 

remove phosphate groups from phosphorylated tyrosine 

residues of proteins. PTPs display diverse structural 

features and play important roles in the regulation of 

cell proliferation, differentiation, cell adhesion and 

motility, and cytoskeletal function. They are either 

transmembrane receptor-like PTPs or cytosolic enzymes. 

Each PTP contains a highly conserved catalytic domain 

of about 240 residues that contains highly conserved 

arginine and cysteine residues at the catalytic domain. 

The diversity of PTPs is primarily due to the variety 

of non-catalytic regulatory sequences and targeting 

domains attached to both N- and C-termini. 

Another category of protein phosphatases is the dual 

specificity phosphatases (DSPs), which play a key role in 

the dephosphorylation of MAP kinases. Hence, they are 

also termed as MAP kinase phosphatases (MKPs). On the 

basis of predicted structures, MKPs have been divided 

into three subgroups. Group I contains DSP1, DSP2, 

DSP4, and DSP5; group II enzymes are DSP6, DSP7, 

DSP9, and DSP10; and group III consists of DSP8 and 

DSP16. All the DSPs share strong amino-acid sequence 

homology in their catalytic domains. The catalytic 

domain contains a highly conserved consensus sequence 

DX 26 (V/L)X(V/ I)HCXAG(I/V) SRSXT(I/V)XXAY(L/I)M, 

where X could be any amino acid. The three underlined 

amino acids are reported to be essential for the catalytic 

activity of DSPs. The cysteine is required for the 

nucleophilic attack on the phosphorus of the substrate 

and the formation of the thiol-phosphate intermediate. 

The conserved arginine binds the phosphate group 

of phosphotyrosine or phosphothreonine, enabling 

transition-state stabilization, and the aspartate enhances 

catalysis by protonating oxygen on the departing 

phosphate group. All DSPs contain two conserved 

regions, known as the CH2 domains, at their amino 

terminus, which are involved in substrate binding. In 

addition, they contain a MAP kinase-docking site at the 

amino terminus that consists of a cluster of positively 

charged amino acids. The corresponding docking site 

on MAP kinases consists of negatively charged residues 

indicating that electrostatic interactions are involved in 

binding of MAP kinases and MKPs. The group III DSPs 

also have an extended carboxy terminus containing 

PEST sequences (abundant in proline, glutamate, serine 

and threonine) that are commonly found in rapidly 

degrading proteins. Removal of PEST sequences results 

in their stabilization. 

References: 

ATP ADP 

Stocker, A.W. 2005. J. Endocrinol. 185, 9. 

Faroog, A., and Zhou, M.M. 2004. Cell Signal. 16, 769. 

Bollen, M., and Beullens, M. 2002. Trends Cell Biol. 12, 38. 

Goldstein, B.J. 2002. J. Clin. Endocrinol. Metab. 87, 2474. 

Klumpp, S., and Krieglstein J. 2002. Curr. Opin. Pharmacol. 2, 458. 

Berndt, N. 999. Front. Biosci. 4, 22. 

Oliver, C.J., and Shenolikar, S. 998. Front. Biosci. 3, D96 . 

Theodosiou, A., and Ashworth, A. 2002. Genome Biol. 3, 3009. . 

Neel, B.G., and Tonks, N.K. 997. Curr. Opin. Cell Biol. 9, 93. 

Stone, R.L., and Dixon, J.E. 994. J. Biol. Chem. 269, 3 323. 

58 Orders Phone 800 854 34 7 


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Protein 

P i 

Ser 

Thr 

Tyr 

Protein 

Phosphatase 

Protein 

More online... www.calbiochem.com/inhibitors/PP 

Ser 

Thr 

Tyr 

P

Protein Phosphatase Inhibitors 




bpV(bipy) 203694 [Potassium Bisperoxo(bipyridine)oxovanadate (V)] 

A potent protein tyrosine phosphatase (PTP) inhibitor (K i = 00 nM for insulin 

receptor dephosphorylation). 

bpV(HOpic) 203701 [Dipotassium Bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate (V)] 

A potent protein tyrosine phosphatase (PTP) inhibitor. 

bpV(phen) 203695 [Potassium Bisperoxo(1,10-phenanthroline)oxovanadate (V)] 

A potent protein tyrosine phosphatase (PTP) inhibitor. Exhibits 000-fold potency 

over sodium orthovanadate. 

bpV(pic) 203705 [Dipotassium Bisperoxo(picolinato)oxovanadate (V)] 

A potent protein tyrosine phosphatase (PTP) inhibitor. 

Calcineurin 

Autoinhibitory Peptide 

Calcineurin 

Autoinhibitory Peptide, 

Cell-permeable 

Calyculin A, 

Discodermia calyx 

207000 (ITSFEEAKGLDRINERMPPRRDAMP) 

A specific calcineurin inhibitor (PP2B) that blocks Mn 2+ -stimulated PP2B activity 

(IC 50 = 0 mM). 

207001 (11R-CaN-AID; Ac-RRRRRRRRRRRGGGRMAPPRRDAMPSDA-NH 2 ) 

A cell-permeable peptide composed of the calcineurin (CaN) autoinhibitory domain 

(AID) fused to a poly-arginine-based protein transduction domain ( R) that inhibits 

CaN phosphatase activity. 

208851 A cell-permeable phosphorylated polyketide that inhibits PP2A ~PP >> PP2B 

(IC 50 for PP2A = 0.5 - .0 nM and for PP = 2.0 nM). 

Cantharidic Acid 210150 (5´-3´2,3-Dicarboxy-2,3-dimethyl-1,4-epoxycyclohexane; exo-1,6-Dicarboxy-endo-1, 

6-dimethyl-7-oxabicylco[2,2,1]heptane) 

A terpenoid compound with high selectivity for PP2A (IC = 50 nM). 

50 

Cantharidin 210155 (Hexahydro-3a,7a-dimethyl-4,7-epoxyisobenzofuran-1,3-dione) 

A cell-permeable terpenoid that inhibits PP2A > PP >> PP2B (IC 50 for PP2A = 40 nM 

and for PP = 473 nM). 

CDC25 Phosphatase 

Inhibitor, BN82002 

CDC25 Phosphatase 

Inhibitor, NSC 663284 

Cyclosporin A, 

Tolypocladium inflatum 

217691 [N-(2-Hydroxy-3-methoxy-5-dimethylamino)benzyl, N´-(2-(4-nitrophenethyl)), 

N´´-methylamine] 

A cell-permeable, ortho-hydroxybenzylamino compound that acts as a potent, selective 

and irreversible inhibitor of CDC25 phosphatase family (IC in mM = 2.4, 3.9, 6.3, 5.4, 

50 

and 4.6 for 25A, 25B2, 25B3, 25C, and 25C-cat, respectively). Displays ~20-fold greater 

selectivity for CDC25 phosphatases over CD45 tyrosine phosphatase. 

217692 [6-Chloro-7-(2-morpholin-4-yl-ethylamino)quinoline-5,8-dione; DA3003-1] 

A cell-permeable, 7-substituted quinolinedione compound that acts as a potent, 

irreversible and mixed competitive inhibitor of the CDC25 phosphatase family (K i = 

29 nM, 95 nM and 89 nM for CDC25A, CDC25B2 and CDC25C, respectively; IC 50 = 

2 0 nM for CDC25B2) and displays nearly 20- and 450-fold greater selectivity for the 

CDC252 phosphatases over VHR and PTP B (IC 50 = 4.0 mM and > 00 mM, respectively). 

5 mg $ 0 

5 mg $ 5 

0 mg $ 27 

5 mg $ 2 

250 mg $97 

mg $ 63 

0 mg $ 2 

0 mg $63 

20 mg $58 

5 mg $90 

5 mg $ 42 

239835 Binds to cyclophilin in cells; the complex inhibits PP2B with nanomolar affinity. 00 mg $68 

Cypermethrin 239900 [(R,S)-a-Cyano-3-phenoxybenzyl-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate] 

A potent inhibitor of PP2B (IC 50 = 40 pM). 

DARPP-32, Rat, 

Recombinant, E. coli 

DARPP-32, Phospho-, 

Rat, Recombinant, 

E. coli 

251755 (Dopamine- and cAMP-regulated Phosphoprotein) 

An inhibitor of PP (IC 50 = –2 mM). 

251756 (Phospho-dopamine- and cAMP-regulated Phosphoprotein) 

A potent inhibitor of PP (IC 50 = nM). 

Deltamethrin 253300 [(S)-a-Cyano-3-phenoxybenzyl(1R)-cis-3-(2,2-dibromovinyl)-2,2dimethylcyclopropanecarboxylate] 

A potent inhibitor of PP2B (IC = 00 pM). 

50 

0 mg $69 

00 mg $2 

30 mg $240 

0 mg $90 

Dephostatin 263200 A protein tyrosine phosphatase (PTP) inhibitor (IC 50 = 7.7 mM). mg $93 

3,4-Dephostatin 263202 (3,4-Dihydroxy-N-methyl-N-nitrosoaniline) 

A protein tyrosine phosphatase inhibitor (IC 50 = 8 mM). 

3,4-Dephostatin, Ethyl- 263203 A more stable ethyl analog of the protein tyrosine phosphatase (PTP) inhibitor 3, 

4-Dephostatin (Cat. No. 263202). Potently inhibits PTP B (IC 50 = 3. 8 mM). 

mg $ 73 

mg $ 30 


Phone 800 628 8470 


59


Protein Phosphatase Inhibitors, continued 


,4-Dimethylendothall 311250 (1,4-Dimethyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic Acid) 

A useful negative control for Canthardic Acid (Cat. No. 2 0 50), Canthardin 

(Cat. No. 2 0 55), and Endothall (Cat. No. 324760). 

N eIF-2a Inhibitor, 

Salubrinal 

324895 (Sal) 

A cell-permeable thiourea compound that acts as a selective inhibitor of eukaryotic 

translation initiation factor 2 subunit a (eIF-2a) dephosphorylation by phosphatase 

complexes. 

Endothall 324760 (7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic Acid) 

A specific inhibitor of PP2A (IC 50 = 90 nM). 

Fenvalerate 341380 [a-Cyano-3-phenoxybenzyl-a-(4-chlorophenyl)isovalerate] 

A potent inhibitor of PP2B (IC 50 = 2–4 nM). 

Fostriecin, Sodium 

Salt, Streptomyces 

pulveraceous 

b-Glycerophosphate, 

Disodium Salt, 

Pentahydrate 

Microcystin-LF, 

Microcystis aeruginosa 

Microcystin-LR, 


InSolution 

Microcystin-LR, 


Microcystin-LW, 


Microcystin-RR, 


344280 (FST; Phosphotrienin) 

A potent PP2A inhibitor (IC 50 = 3.2 nM). Inhibits PP only at higher concentrations 

(IC 50 = 3 mM). 

35675 A phosphate group donor in matrix mineralization studies that acts as a protein 

phosphatase inhibitor. 

475814 A more cell-permeable analog of Microcystin-LR (Cat. No. 4758 5). Useful for studies 

in intact cells. Not available for sale outside the United States. 

475815 A cyclic peptide that inhibits PP2A~PP >> PP2B (IC 50 for PP2A = 40 pM and for 

PP = .7 nM). Does not enter some mammalian cells. Not available for sale outside 

the United States. 

475821 A 2.5 mM (250 mg/ 00 ml) of Microcystin-LR, Microcystis aeurginosa 

(Cat. No. 4758 5) in DMSO. Not available for sale outside the United States. 

475818 A more cell-permeable analog of Microcystin-LR (Cat. No. 4758 5). Useful for studies 

in intact cells. Not available for sale outside the United States. 

475816 A cyclic peptide that inhibits PP2A~PP >> PP2B (IC 50 = .4 mM). Does not enter some 

mammalian cells. Not available for sale outside the United States. 

mpV(pic) 475950 [Monoperoxo(picolinato)oxovanadate(V)] 

A potent PTP inhibitor. More potent for insulin receptor (IR) dephosphorylation than 

EGFR dephosphorylation. 

a-Naphthyl 

Acid Phosphate, 

Monosodium Salt 

NFAT Activation 


NIPP- , His•Tag®, 

Bovine Thymus, 


Okadaic Acid, 

Prorocentrum 

concavum 

N InSolution Okadaic 

Acid, Prorocentrum 

concavum 

Okadaic Acid, 

Ammonium Salt 

0 mg $76 

5 mg $ 29 

20 mg $55 

25 mg $55 

0 mg $ 7 

60 Orders Phone 800 854 34 7 


Fax 800 776 0999 


50 g 

00 g 

250 g 

$32 

$48 

$98 

25 mg $ 4 

500 mg $ 78 

250 mg $ 0 

25 mg $ 5 

250 mg $202 

0 mg $ 7 

479775 A broad-spectrum protein phosphatase inhibitor. 5 g $44 

480403 INCA-6; Inhibitor of NFAT-Calcineurin Association-6 

A cell-permeable quinone compound that acts as a potent and selective inhibitor of 

Calcineurin-NFAT (Nuclear Factor of Activated T cells) signaling. Binds to calcineurin with 

high affinity (K d = 800 nM), disrupts its interaction with NFAT and completely blocks its 

dephosphorylation, nuclear import of NFAT (~40 mM in C .7W2 T cells), and induction of 

cytokine mRNAs. Unlike CsA (Cat. No. 239835) and FK506, INCA-6 does not affect calcineurin 

activity or its downstream signaling. 

482251 (Nuclear Inhibitor of Protein Phosphatase-1) 

A potent and specific inhibitor or protein phosphatase (PP ; K i = – 0 pM) that can be used 

to distinguish PP from other major serine/threonine protein phosphatases, including PP2A, 

PP2B, and PP2C. 

495604 (OA) 

A cell-permeable inhibitor of PP2A > PP >> PP2B. (IC 50 for PP2A = 00 pM; 

for PP = 0– 5 nM; and for PP2B = 5 mM). 

495609 A 250 mM (25 mg/ 24 ml) solution of Okadaic Acid, Prorocentrum concavum 


459616 A water-soluble form of Okadaic Acid (Cat. No. 495604). Inhibits protein phosphatases 

and 2A. 

5 mg $90 

0 mg 

25 mg 

00 mg 

mg $95 

$40 

$65 

$2 2 

25 mg $65 

25 mg $60





Okadaic Acid, 

Potassium Salt 

Okadaic Acid, Sodium 

Salt 


and 2A. 


and 2A. 

Phenylarsine Oxide 521000 (Oxophenylarsine; PAO) 

A membrane-permeable protein tyrosine phosphatase inhibitor (IC 50 = 8 mM). 

Stimulates 2-deoxyglucose transport in insulin-resistant human skeletal muscle and 

activates p56 lck protein tyrosine kinase. Blocks TNF-a-dependent activation of NF-kB in 

human myeloid ML- a cells. PAO inhibits the protease activities of recombinant human 

caspases as well as endogenous caspases that are active in extracts of pre-apoptotic 

chicken DU249 cells (S/M extracts). 

5-Phosphatase Inhibitor 524620 [(1R,2R,4R)-Cyclohexane-1,2,4-tris(methylenesulfonate)] 

Inhibits 5-phosphatase-catalyzed dephosphorylation of Ins( ,4,5)P 3 (K i = 4 mM). 

Protein Phosphatase 

Inhibitor 2, Human, 


Protein Phosphatase 

Inhibitor 2, Rabbit 

Muscle, Recombinant, 

E. coli 

Protein Phosphatase 2A 

Inhibitor I PP2A , Human 

Kidney, Recombinant, 

E. coli 

Protein Phosphatase 2A 

PP2A Inhibitor I , Human, 

2 


Protein Tyrosine 

Phosphatase Inhibitor I 


Phosphatase Inhibitor II 


Phosphatase Inhibitor 

III 


Phosphatase Inhibitor 

IV 


Phosphatase CD45 


539638 (I-2; Inhibitor-2) 

Potently inhibits the activity of the free catalytic subunit of PP (IC 50 = nM). 

539516 (PPI-2) 

Inhibits the catalytic subunit of PP (IC 50 = 2 nM). 

50 mg $93 

25 mg $60 

250 mg $34 

mg $60 

00 mg $20 

20 mg $202 

539552 Potently inhibits all forms of PP2A (K i = ~ 00 pM). 250 ng $209 

PP2A 539620 (I ) 2 

Potently inhibits PP2A (K = ~ 00 pM). 

i 

540200 (a-Bromo-4-hydroxyacetophenone; 4-Hydroxyphenacyl Br) 

A potent, cell-permeable, covalent PTP inhibitor. 

540205 (a-Bromo-4-methoxyacetophenone; 4-Methoxyphenacyl Br) 


540210 [a-Bromo-4-(carboxymethoxy)acetophenone; 4-(Carboxymethoxy)phenacyl Br] 


540211 [bis(4-Trifluoromethylsulfonamidophenyl)-1,4-diisopropylbenzene] 

A potent, reversible, substrate competitive, active-site-directed inhibitor of protein tyrosine 

phosphatases (PTP). Reported to inhibit SHP-2 (IC 50 = .8 mM), PTP B (IC 50 = 2.5 mM), PTP-e 

(IC 50 = 8.4 mM), PTP-Meg-2 (IC 50 = 3 mM), PTP-s (IC 50 = 20 mM), PTP-b (IC 50 = 6.4 mM), and 

PTP-m (IC 50 = 6.7 mM). 

540215 [N-(9,10-Dioxo-9,10-dihydro-phenanthren-2-yl)-2,2-dimethyl-propionamide; 

PTPase CD45 Inhibitor] 

A cell-permeable, potent, selective, competitive, and reversible inhibitor of CD45 

(IC = 200 nM using pNPP as the substrate, 3.8 mM for CD45 lck, > 30 mM for PTP B lck). 

50 

PTP B Inhibitor 539741 [3-(3,5-Dibromo-4-hydroxy-benzoyl)-2-ethyl-benzofuran-6-sulfonicacid- 

(4-(thiazol-2-ylsulfamyl)-phenyl)-amide] 

A cell-permeable, selective, reversible and non-competitive allosteric inhibitor of PTP B 

(IC = 4 mM and 8 mM for PTP B and PTP B , respectively). Binds to a novel site 

50 403 298 

away from the catalytic pocket and inhibits PTP B activity by preventing closure of the 

WPD loop. 

RK-682, Streptomyces 

sp. 

557322 (3-Hexadecanoyl-5-hydroxymethyl-tetronic Acid) 

A specific non-cell-permeable inhibitor of PTP. Inhibits dephosphorylation activity of 

CD45 (IC 50 = 54 mM) and VHR (IC 50 = 2.0 mM) in vitro. 

Sodium Orthovanadate 567540 Inhibitor of protein tyrosine phosphatases of general/broad specificity; potent inhibitor 

of alkaline phosphatase. 

250 ng $209 

0 mg $ 8 

25 mg $43 

0 mg $ 8 

0 mg $84 

mg $ 36 

5 mg $ 63 

200 mg $ 03 

5 g $36 


Phone 800 628 8470 


6




Sodium Stibogluconate 567565 (Antimony Sodium Gluconate; NaSb v ; SSG) 

An irreversible inhibitor of (PTPase), including Src homology PTPase- (SHP- ). Exhibits 

anti-leishmanial properties. At higher concentrations, inhibits SHP-2 and PTP B activities. 

Suramin, Sodium Salt 574625 Useful as a reversible and competitive inhibitor of protein tyrosine phosphatases. 50 mg 

200 mg 

N InSolution 

Tautomycetin, S. 

griseochromogenes 

N 

Tautomycin, 

Streptomyces 

spiroverticillatus 

Phosphatase Inhibitor Cocktail Set I 

A cocktail of three phosphatase inhibitors that will inhibit alkaline 

phosphatases as well as serine/threonine protein phosphatases such 

as PP and PP2A. This product is provided as a set of five ml vials. 

Each vial contains ml of phosphatase inhibitor cocktail solubilized 

in DMSO with the following components: Bromotetramisole oxalate 

(0.5 mM), Cantharidin (Cat. No. 2 0 55; 500 mM), and Microcystin- 

LR (Cat. No. 4758 5; 500 nM). Not available for sale outside the 

United States. 

Cat. No. 524624 1 set $170 

Phosphatase Inhibitor Cocktail Set II 

A cocktail of five phosphatase inhibitors for the inhibition of acid 

and alkaline phosphatases as well as protein tyrosine phosphatases 

(PTPs). Suitable for use with tissue and cell extracts, including 

extracts containing detergents. Provided as a set of five vials, with 

each vial containing ml aqueous solution of 200 mM Imidazole, 

00 mM Sodium Fluoride, 5 mM Sodium Molybdate, 00 mM 

Sodium Orthovanadate, and 400 mM Sodium Tartrate Dihydrate. 

Cat. No. 524625 1 set $213 

Phosphatase Inhibitor Cocktail Set III 

580550 A mM (50 mg/82 ml) solution of Tautomycetin in DMSO. Specifically inhibits PP 

activity with ~38-fold greater selectivity over PP2A (IC 50 = .6 nM for PP and 62 nM 

for PP2A). Further, inhibits PP5 at higher concentrations (IC 50 ~ mM) and only weakly 

affects calcineurin and LDP- at mM. 

580551 A potent inhibitor of PP (IC 50 = nM), PP2A (IC 50 = 0 nM), and smooth muscle 

endogenous phosphatase (IC 50 = 6 nM). 

A cocktail of four phosphatase inhibitors for the inhibition of both 

serine/threonine and protein tyrosine phosphatases. Available as a 

ml vial or as a set of five ml vials. Each vial contains ml 

of aqueous solution with the following components: 50 mM 

Sodium Fluoride, 0 mM b-Glycerophosphate, 0 mM Sodium 

Pyrophosphate Decahydrate, and mM Sodium Orthovanadate. 

Cat. No. 524627 1 ml 

1 set 

$115 

$395 

Phosphatase Inhibitor Cocktail Set IV 

Phosphotyrosine Phosphatase Inhibitor Set 

(Vanadium) 

Contains 5 g of Sodium Orthovanadate (Cat. No. 567540), 

0 mg each of bpV(phen) (Cat. No. 203695) and mpV(pic) 

(Cat. No. 475950). 

Cat. No. 525325 1 set $203 

Protein Phosphatase Inhibitor Set II 

g $75 

Contains 0 mg Cypermethrin (Cat. No, 239900), mg Dephostatin 

(Cat. No. 263200), 0 mg Okadaic Acid (Cat. No. 495604), and mg 

NIPP- , Bovine Thymus. 

Cat. No. 539630 1 set $304 

62 Orders Phone 800 854 34 7 


Fax 800 776 0999 


N 

$34 

$ 

50 mg $ 80 

50 mg $2 7 

A cocktail of three phosphatase inhibitors for the inhibition of both 

serine/threonine and alkaline phosphatases. Available as a ml vial 

or as a set of five ml vials. Each vial contains ml of solution with 

the following components: 500 mM Cantharidin (Cat. No. 2 0 55), 

2.5 mM (-)-p-Bromotetramisole oxalate, and mM Calyculin A, 

Discodermia calyx (Cat. No. 20885 ). 

Cat. No. 524628 1 ml 

1 set 

$75 

$285

Apoptosis 

Caspase Inhibitors 

Activation of caspases is one of the most widely 

recognized features of apoptosis. Caspases are cysteinedependent, 

aspartate-specific proteases. They exist as 

latent precursors, which, when activated by limited 

proteolysis, initiate the death program by destroying 

key components of the cellular infrastructure and 

activating factors that mediate damage to the cells. 

The mechanism of caspase activation appears to be 

conserved in evolution. Thus far, 14 members of the 

caspase family have been identified, 11 of which are 

present in humans. Caspases have been categorized into 

upstream initiators and downstream executioners. A 

distinctive feature of caspases is the absolute requirement 

of an aspartic acid residue in the substrate P 1 position. 

The P 4 residue is important in substrate recognition 

and specificity. Generally, catalysis involves a cysteine 

protease mechanism. The tetrapeptide corresponding to 

the substrate P 4 - P 1 residues is sufficient to recognize 

both caspase-1 and caspase-3. This also forms the basis of 

designing novel inhibitors of caspases. 

Caspase activation is generally considered as the 

"point of no return” in apoptotic pathways. Caspases 

are activated by two major pathways: the receptormediated 

(Fas ligand or TNF-a-mediated) pathway and 


Apoptosis 

the mitochondrial pathway. The receptor-mediated 

pathway leads to the activation of pro-caspase-8. In the 

mitochondrial pathway, pro-apoptotic members of the 

Bcl-2 family associate with mitochondria and direct the 

release of cytochrome c (Cyt c) and other proteins, which 

activate pro-caspase-9. 

Caspase inhibitors act by binding to the active site of 

caspases either in a reversible or irreversible manner. 

Inhibitor design includes a peptide recognition 

sequence attached to a functional group such as 

an aldehyde (CHO), chloromethylketone (CMK), or 

fluoromethylketone (FMK). The peptide recognition 

sequence corresponding to that found in endogenous 

substrates determines the specificity of a particular 

caspase. For example, compounds with the Ac-YVAD- 

CHO sequence are potent inhibitors of caspases-1 

(K i ≈ 10 nM), and exhibit very weak inhibitory effect on 

caspases-3 and -7 (K i ≥ 50 mM). Exclusion of the tyrosine 

residue from the inhibitor peptide results in a potent but 

less specific inhibitor. For example, Z-VAD-FMK inhibits 

not only caspases-1 and -4, but also caspases-3 and -7. 

More online... www.calbiochem.com/inhibitors/caspase 


Phone 800 628 8470 


63

Apoptosis 

Caspase Inhibitors 

Product Cat. No. Sequence 

Cell - 

Permeable 

Reversible? 

Known Target 

Caspases 

(or Granzyme B) 

Size Price 

Caspase Inhibitor I 627610 Z-VAD(OMe)-FMK a Yes No General mg $ 84 

InSolution Caspase Inhibitor I 627609 Z-VAD(OMe)-FMK a Yes No General mg $ 84 

Caspase Inhibitor I, Biotin Conjugate 218742 Biotin-X-VAD(OMe)-FMK a — No General mg $355 

Caspase Inhibitor II 218735 Ac-VAD-CHO ‡ No Yes General mg $65 

Caspase Inhibitor II, 


218830 Ac-AAVALLPAVLLALLAPVAD- 

CHO 

Yes Yes General mg $ 64 

Caspase Inhibitor III 218745 Boc-D(OMe)-FMK a Yes No General 250 mg 

mg 

Caspase Inhibitor IV 218784 Boc-D(OBzl)-CMK b Yes No General 5 mg $60 

Caspase Inhibitor VI 219007 Z-VAD-FMK a — No General 250 mg 

mg 

N InSolution Caspase Inhibitor VI 219011 Z-VAD-FMK a — No General mg $ 82 

Caspase Inhibitor VIII 218729 Ac-VDVAD-CHO No Yes 2, 3, 7 mg $99 

N Caspase Inhibitor X 218723 — No Yes 3, 7, 8 5 mg $ 8 

Caspase Inhibitor, Negative Control 342000 Z-FA-FMK Yes No mg 

5 mg 

Caspase- Inhibitor I 400010 Ac-YVAD-CHO ‡ No Yes , 4 mg 

5 mg 

Caspase- Inhibitor I, 


400011 Ac-AAVALLPAVLLALLAP- 

YVAD-CHO 

64 Orders Phone 800 854 34 7 


Fax 800 776 0999 


$57 

$ 44 

$62 

$ 82 

$77 

$3 3 

$60 

$243 

Yes Yes , 4 mg $ 70 

Caspase- Inhibitor II 400012 Ac-YVAD-CMK b Yes No , 4 5 mg $208 

Caspase- Inhibitor II, Biotin 

Conjugate 

400022 Biotin-YVAD-CMK b — No , 4 5 mg $297 

Caspase- Inhibitor IV 400015 Ac-YVAD-AOM d Yes No , 4 mg $95 

Caspase- Inhibitor V 400019 Z-Asp-CH 2 -DCB e Yes No , 4 5 mg $362 

Caspase- Inhibitor VI 218746 Z-YVAD(OMe)-FMK a Yes No , 4 250 mg 

mg 

Caspase-2 Inhibitor I 218744 Z-VD(OMe)VAD(OMe)-FMK a Yes No 2 250 mg 

mg 

Caspase-2 Inhibitor II 218814 Ac-LDESD-CHO No Yes 2, 3 mg 

5 mg 

Caspase-3 Inhibitor I 235420 Ac-DEVD-CHO ‡ No Yes 3, 6, 7, 8, 0 mg 

5 mg 

Caspase-3 Inhibitor I, Biotin 

Conjugate 

Caspase-3 Inhibitor I, 


InSolution Caspase-3 Inhibitor I, 


$88 

$263 

$ 

$3 0 

$73 

$286 

$68 

$267 

235422 Biotin-DEVD-CHO ‡ — Yes 3, 6, 7, 8, 0 mg $ 7 


DEVD-CHO 


DEVD-CHO 

Caspase-3 Inhibitor II 264155 Z-D(OMe)E(OMe)VD(OMe)- 

FMK a 

InSolution Caspase-3 Inhibitor II 264156 Ac-AAVALLPAVLLALLAP- 

DEVD-CHO 

Caspase-3 Inhibitor II, Biotin 

Conjugate 

218747 Biotin-X- 

D(OMe)E(OMe)VD(OMe)- 

FMK a 

Yes Yes 3, 6, 7, 8, 0 mg $ 56 

Yes Yes 3, 6, 7, 8, 0 mg $ 56 

Yes No 3, 6, 7, 8, 0 250 mg 

mg 

$8 

$227 

Yes Yes 3, 6, 7, 8, 0 250 mg $83 

— No 3, 6, 7, 0 mg $366 

Caspase-3 Inhibitor III 218750 Ac-DEVD-CMK b Yes No 3, 6, 7, 8, 0 mg 

5 mg 

Caspase-3 Inhibitor IV 235421 Ac-DMQD-CHO ‡ No Yes 3 mg 

5 mg 

Caspase-3 Inhibitor V 219002 Z-D(OMe)QMD(OMe)-FMK Yes No 3 mg $238 

Key: a: FMK = Fluoromethyl ketone; b: CMK = Chloromethyl ketone; c: FAOM = 2,6-bis(trifluoromethyl) benzoyloxymethyl ketone; d: AOM = 2,6dimethylbenzoyloxy 

ketone; e: DCB = 2,6 dichlorobenzoyloxy; ‡: These aldehyde-based inhibitors may be cell-permeable, albeit to a lesser extent. 

$66 

$26 

$83 

$275

Caspase Inhibitors, continued 

Product Cat. No. Sequence 


Cell - 

Permeable 

Reversible? 

Known Target 

Caspases 

(or Granzyme B) 

Apoptosis 

Size Price 

N Caspase-3 Inhibitor VII 219012 — Yes Yes 3 mg $ 35 

Caspase-3/7 Inhibitor I 218826 — Yes Yes 3, 7 mg $96 

N Caspase-3/7 Inhibitor II 218832 Ac-DNLD-CHO ‡ No Yes 3, 7, 8, 9 mg $90 

Caspase-4 Inhibitor I 218755 Ac-LEVD-CHO ‡ No Yes 4 mg $62 




LEVD-CHO 

Yes Yes 4 mg $ 65 

Caspase-5 Inhibitor I 218753 Z-WE(OMe)HD(OMe)-FMK a Yes No , 4, 5 250 mg 

mg 

Caspase-6 Inhibitor I 218757 Z-VE(OMe)ID(OMe)-FMK a Yes No 6 250 mg 

mg 

Caspase-6 Inhibitor II, 





VEID-CHO 


IETD-CHO 

$ 3 

$3 9 

$92 

$26 


Yes Yes 8, Granzyme B mg $ 70 

Caspase-8 Inhibitor II 218759 Z-IE(OMe)TD(OMe)-FMK a Yes No 8, Granzyme B 250 mg 

mg 

InSolution Caspase-8 Inhibitor II 218840 Z-IE(OMe)TD(OMe)-FMK a Yes No 8, Granzyme B 250 mg $88 

Caspase-9 Inhibitor I 218761 Z-LE(OMe)HD(OMe)-FMK a Yes No 9 250 mg 

mg 

InSolution Caspase-9 Inhibitor I 218841 Z-LE(OMe)HD(OMe)-FMK a Yes No 9 250 mg $ 3 

Caspase-9 Inhibitor II, 



LEHD-CHO 

$88 

$263 

$ 3 

$3 0 


Caspase-9 Inhibitor III 218728 Ac-LEHD-CMK Yes No 9 mg $87 

Caspase- 3 Inhibitor I 219005 Ac-LEED-CHO ‡ No Yes 3 mg $43 

Caspase- 3 Inhibitor II 219009 Z-LE(OMe)E(OMe)D(OMe)- 

FMK a 

Yes No 3 250 mg 

mg 

CrmA, Recombinant PF122 — No — , Granzyme B 00 mg $5 0 

Granzyme B Inhibitor I 368050 Z-AAD-CMK b Yes No Granzyme B mg $69 

Granzyme B Inhibitor II 368055 Ac-IETD-CHO ‡ No Yes 8, Granzyme B mg $60 

Granzyme B Inhibitor IV 368056 Ac-IEPD-CHO No Yes 8, Granzyme B mg $84 

Group III Caspase Inhibitor I 368620 Z-A-E(OMe)-V-D(OMe)-FMK a Yes No 6, 8, 9, 0 mg $27 

InSolution Q-VD-OPh, Non-Omethylated 

$83 

$249 

551476 Q-Val-Asp-CH2-Oph Yes No 3, 8, 9, 0, 2 mg $ 42 

XIAP, Human, Recombinant, E. coli PF137 — No — 3, 7 50 mg $386 

Key: a: FMK = Fluoromethyl ketone; b: CMK = Chloromethyl ketone; c: FAOM = 2,6-bis(trifluoromethyl) benzoyloxymethyl ketone; d: AOM = 2,6dimethylbenzoyloxy 

ketone; e: DCB = 2,6 dichlorobenzoyloxy; ‡: These aldehyde-based inhibitors may be cell-permeable, albeit to a lesser extent. 


Phone 800 628 8470 


65

Apoptosis 

Caspase Inhibitors, continued 

Caspase Inhibitor Set I 

A set of 3 separate vials. Each set contains mg each of Caspase-3 

Inhibitor II, Z-DEVD-FMK (Cat. No. 264 55); Caspase- Inhibitor I, 

Ac-YVAD-CHO (Cat. No. 4000 0); and Caspase Inhibitor I, Z-VAD-FMK 

(Cat. No. 6276 0). 

Cat. No. 235429 1 set $398 

Caspase Inhibitor Set II 

A set of 8 separate vials of cell-permeable, irreversible caspase 

inhibitors. Each set contains 250 µg each of Caspase- Inhibitor VI, 

Z-YVAD-FMK (Cat. No. 2 8746); Caspase-2 Inhibitor I, Z-VDVAD- 

FMK (Cat. No. 2 8744); Caspase-3 Inhibitor II, Z-DEVD-FMK (Cat. 

No. 264 55); Caspase-5 Inhibitor I, Z-WEHD-FMK (Cat. No. 2 8753); 

Caspase-6 Inhibitor I, Z-VEID-FMK (Cat. No. 2 8757); Caspase-8 

Inhibitor II, Z-IETD-FMK (Cat. No. 2 8759); Caspase-9 Inhibitor I, 

Z-LEHD-FMK (Cat. No. 2 876 ); and Caspase Inhibitor III, Boc-D-FMK 

(Cat. No. 2 8745). 

Cat. No. 218772 1 set $603 

Granzyme Inhibitors 




218773 (granzyme B Inhibitor II, Cell-permeable; IETD-CHO, Cell-permeable) 

A potent, cell-permeable and reversible inhibitor of caspase-8 

(FLICE, MACH, Mch5) and granzyme B. 

Caspase-8 Inhibitor II 218759 [granzyme B Inhibitor III; Z-IE(OMe)TD(OMe)-FMK] 

A potent, cell-permeable, irreversible inhibitor of caspase-8 and granzyme B. 

InSolution Caspase-8 


218840 [granzyme B Inhibitor III; Z-IE(OMe)TD(OMe)-FMK] 

A 5 mM (250 mg/76 ml) solution of caspase-8 Inhibitor II (Cat. No. 2 8759) 

in anhydrous DMSO. 

mg $ 70 

66 Orders Phone 800 854 34 7 


Fax 800 776 0999 


250 mg 

mg 

$88 

$263 

250 mg $88 

CrmA, Recombinant PF122 An inhibitor of caspase- and granzyme B. 00 mg $5 0 

Granzyme B Inhibitor I 368050 (Z-AAD-CMK) 

A weak inhibitor of human and murine granzyme B. Also inhibits the apoptosis related 

DNA fragmentation in lymphocytes by fragmentin 2, a rat lymphocyte granule protease 

homologous to granzyme B (ID 50 = 300 nM). 

Granzyme B Inhibitor II 368055 (Ac-IETD-CHO; Caspase-8 Inhibitor I) 

A potent, reversible inhibitor of granzyme B and caspase-8. 

Granzyme B Inhibitor IV 368056 (Ac-IEPD-CHO; Caspase-8 inhibitor III) 

A reversible inhibitor of granzyme B that also inhibits caspase-8. 

More online... www.calbiochem.com/inhibitors/granzyme 

Caspase Inhibitor Set III 

A set of 8 separate vials. Each set contains a ready-to-use DMSO 

solution of cell-permeable, irreversible inhibitors of various members of 

the caspase-family proteases. Contains 25 µl (2 mM) each of Caspase- 

Inhibitor VI, Z-YVAD-FMK (Cat. No. 2 8746); Caspase-2 Inhibitor I, 

Z-VDVAD-FMK (Cat. No. 2 8744); Caspase-3 Inhibitor II, Z-DEVD- 

FMK (Cat. No. 264 55); Caspase-5 Inhibitor I, Z-WEHD-FMK (Cat. 

No. 2 8753); Caspase-6 Inhibitor I, Z-VEID-FMK (Cat. No. 2 8757); 

Caspase-8 Inhibitor II, Z-IETD-FMK (Cat. No. 2 8759); Caspase-9 

Inhibitor I, Z-LEHD-FMK (Cat. No. 2 876 ); and Caspase Inhibitor I, 

Z-VAD-FMK (Cat. No. 6276 0). 

Cat. No. 218806 1 set $582 

Caspase Inhibitor Set IV 

A set of 6 separate vials. Each set contains a ready-to-use solution of cellpermeable 

caspase inhibitors and an apoptosis inducer. Contains 25 µl of a 

0 mM solution in DMSO of Caspase-3 Inhibitor II, Z-DEVD-FMK (Cat. No. 

264 55); Caspase-8 Inhibitor II, Z-IETD-FMK (Cat. No. 2 8759); Caspase-9 

Inhibitor I, Z-LEHD-FMK (Cat. No 2 876 ); general caspase inhibitor, 

Z-VAD-FMK (Cat. No. 6276 0); the negative control Z-FA-FMK (Cat. 

No. 342000), and an aqueous solution ( 00 µl, 0.5 µM) of an apoptosis 

inducer, Doxorubicin, Hydrochloride (Cat. No. 324380). 

Cat. No. 218825 1 set $325 

mg $69 

mg $60 

mg $84

Other Selected Inhibitors of Apoptosis 


Apoptosis 


Apoptosis Inhibitor 178488 [M50054; 2,2´-Methylenebis(1,3-cyclohexanedione)] 

A cell-permeable inhibitor of apoptosis induction (IC 50 = 283 mM in FasL-stimulated 

WC8 cells, 550 mM in etoposide-stimulated U937 cells). The anti-apoptotic effects 

are attributed to the inhibition of caspase-3 activation (IC 50 = 334 mM in etoposidestimulated 

U937 cells). 

Apoptosis Inhibitor II, 

NS3694 

178494 (NS3694) 

A cell-permeable compound that specifically prevents the active ~700 kDa apoptosome 

complex formation triggered by cytochrome c release. Protects against apoptosomemediated 

caspase activation and cell death. 

Bax Channel Blocker 196805 [(±)-1-(3,6-Dibromocarbazol-9-yl)-3-piperazin-1-yl-propan-2-ol, bis TFA] 

A cell-permeable dibromocarbazolo-piperazinyl derivative that displays anti-apoptotic 

properties. Effectively blocks Bid-induced cyctochrome c release from HeLa cell 

mitochondria (~80% inhibition at 5 mM) by inhibiting Bax channel-forming activity 

(IC 50 = 520 nM in a liposome channel assay). 

Bax-Inhibiting Peptide, 

V5 

Bax-Inhibiting Peptide, 


Fas/FasL Antagonist, 

Kp7-6 

Humanin, Human, 

Synthetic 

Omi/HtrA2 Protease 

Inhibitor, Ucf- 0 

196810 (BIP-V5; H-VPMLK-OH) 

A cell-permeable pentapeptide based on the Ku70-Bax inhibiting domain that offers 

cytoprotection. Functions as effectively as the Caspase Inhibitor VI (Z-VAD-FMK; Cat. 

No. 2 9007) for Bax-mediated apoptosis (~50–200 mM). 

196811 (BIP-NC; H-IPMIK-OH) 

A cell-permeable mutated analog of the Bax-Inhibiting Peptide, V5 (Cat. No. 968 0) 

that serves as a negative control. Does not suppress Bax-mediated apoptosis (~200 mM). 

341291 (H-YC*DEHFC*Y-OH, Cyclic [Cys-Cys disulfide]; Kp7-6) 

Specifically antagonizes Fas/FasL-mediated cellular apoptotic signals (58% reduction 

of FasL-induced apoptosis in Jurkat cells at mg/ml). Binds to FasL (Cat. Nos. PF033 

and PF092) and Fas (CD95/APO- ) with comparable affinity (K = .2 and 3.2 mM, 

d 


400140 (H-MAPRGFSCLLLLTSEIDLPVKRRA-OH; HN) 

An anti-apoptotic peptide that when expressed intracellularly, offers protection against 

neuronal apoptosis induced by presenilin and APP mutants associated with familial 

Alzheimer’s disease (AD). Reduces cytochrome c release in vitro by directly binding to Bax 

(K ~2 nM). 

d 

496150 {High Temperature Requirement A2 Inhibitor I; 5-[5-(2-Nitrophenyl)furfurylidine]-1,3diphenyl-2-thiobarbituric 

Acid} 

A cell-permeable furfurylidine-thiobarbituric acid compound that acts as a potent, 

specific, competitive, and reversible inhibitor of the pro-apoptotic, heat-inducible, 

mitochondrial serine protease Omi/HtrA2 (IC = 9.5 mM for His-Omi ). Shows very 

50 34-458 

little activity against various other serine proteases tested (IC ≥ 200 mM). Reported to 

50 

block Omi/HtrA2 induced cell death in caspase-9 (-/-) null fibroblasts. 

Pifithrin-a 506132 [2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone, HBr] 

A cell-permeable chemical inhibitor of p53. Reversibly inhibits p53-dependent 

transactivation of p53-responsive genes and reversibly blocks p53-mediated apoptosis. 

Pifithrin-a, Cyclic- 506134 {2-(4-Methylphenyl)imidazo[2,1-b]-5,6,7,8-tetrahydrobenzothiazole, HBr; QB102} 

A cell-permeable and very stable analog of Pifithrin-a (Cat. No. 506 32) with similar 

biological functions, but with reduced cytotoxicity. Reversibly blocks p53-mediated 

apoptosis. 

0 mg $96 

0 mg $ 00 

5 mg $84 

5 mg $84 

5 mg $84 

25 mg $237 

mg $252 

0 mg $98 

5 mg 

0 mg 

$65 

$ 2 

0 mg $ 27 


Phone 800 628 8470 


67

Apoptosis 

Necrosis Inhibitors 


N Necrosis Inhibitor, 

IM-54 

480060 2-(1H-Indol-3-yl)-3-pentylamino-maleimide 

A cell-permeable, mono-indolylmaleimide compound that selectively blocks oxidative 

stress-induced necrotic cell death (~3 mM IM-54 prevented ~50% cell death in HL60 

cells exposed to 00 mM H 2 O 2 ). Does not offer protection against Etoposide- 

(Cat. No. 34 205) induced apoptosis or display antioxidant properties. 

N Necrostatin- 480065 5-(Indol-3-ylmethyl)-(2-thio-3-methyl)hydantoin; Nec-1; Necroptotic Inhibitor, Nec-1 

A cell-permeable, potent, and selective blocker of necroptosis, a non-apoptotic necrotic 

cell-death pathway mediated by death-domain receptors (DRs), in vitro (EC 50 = 494 nM 

in FADD-deficient Jurkat cells treated with TNF-a). Also shown to offer neuroprotection 

in a mouse model of ischemic brain injury. Does not disrupt normal cellular physiology or 

exhibit any effects on apoptosis, autophagy, or oxidative stress-induced necrosis. 

N Necrostatin- , 

Inactive Control 

480066 5-(Indol-3-ylmethyl)-2-thiohydantoin, Nec-1i 

A cell-permeable, analog of Nec- (Cat. No. 480065) that is devoid of antinecroptotic 

properties and serves as a suitable inactive control. 

inNovations 

Each inNovations newsletter presents 

the latest Novagen® products as used 

in research applications. 

• research articles from our scientists and our customers 

• answers from our technical service scientists 

• Novagen product usage in peer-reviewed journals 

• detailed product descriptions 

5 mg $ 39 

5 mg $82 

5 mg $82 

NEW products, 

NEW applications! 

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Fax 800 776 0999 



Cell Division/Cell Cycle/Cell Adhesion 


Cell Adhesion Inhibitors 

Cell adhesion is crucial in the formation and maintenance 

of coherent multi-cellular structures. Two 

major types of cell adhesion processes are seen in multicellular 

organisms: cell-cell adhesion where physical 

bonds are formed between adjacent cells, and cell-matrix 

adhesion where cells bind to adhesive proteins in the 

extracellular matrix (ECM). A wide variety of adhesion 

molecules have been identified that fall into four major 

categories: cadherins, immunoglobulin (Ig)-like adhesion 

molecules, integrins, and selectins. Cell adhesion 

proteins are often transmembrane receptors that have 

domains extending into both the extracellular space and 

the intracellular space. 

Cadherins are the main mediators of Ca 2+ -dependent cellcell 

adhesion. Cadherin-mediated cell-cell adhesion is 

accomplished by homophilic protein-protein interactions 

between two cadherin molecules on cell surface. This 

interaction is mediated by interactions between the 

His-Ala-Val domains and between Trp residues and 

hydrophobic pockets in amino-terminal cadherin 

domains. Cadherins are critical in segregating embryonic 

cells into tissues. 

The Ig superfamily of cell adhesion molecules (CAM) 

is expressed in a wide variety of cell types, including 

neurons, leukocytes, epithelial, and endothelial cells. 

Collectively, they function by both homophilic and 

heterophilic binding. Their heterogeneous expression 

pattern implicates them in diverse biological processes, 

such as brain development, immune responses, tissue 

sorting, morphogenesis, and development of the vascular 

network. They are characterized by the presence of one 

or more Ig-like domain in their extracellular region. 

In addition, the ectodomain of Ig-CAMs may contain 

various numbers of fibronectin type III (FNIII) repeats, 

which possess the Arg-Gly-Asp (RGD) cell attachment 

site. Neural cell adhesion molecules (N-CAMs) and the 

intercellular cell adhesion molecules (ICAMs) are the beststudied 

members of this family. 

Integrins belong to a superfamily of non-covalently bound 

heterodimeric membrane receptor glycoproteins. They are 

composed of a variable a-subunit of 150-170 kDa and a 

conserved 95 kDa b-subunit. Although both subunits are 

required for adhesion, the binding specificity primarily 

depends on the extracellular portion of the a-subunit. 

While generally classified as adhesion molecules, integrins 

also play an important role in signal transduction. Signal 

transduction through integrins occurs in two directions: 

from the extracellular microenvironment into the cell 

(outside-in signaling), and from the cytoplasm to the 

extracellular domain of the receptor (inside-out signaling). 

Among the signaling molecules involved in integrinmediated 

cell survival is focal adhesion kinase (FAK), 

which is activated following integrin ligation. It activates 

downstream survival pathways, such as PI 3-kinase, Akt, 

and MAPK/ERK. In response to specific stimuli, integrins 

that are generally diffused over the cell surface cluster in 

focal contacts. Their combined affinities create a region 

with sufficient adhesive capacity to adhere to the ECM. This 

allows cells to bind to a large numbers of matrix molecules 

simultaneously while still maintaining their ability to 

explore their environment. 

Selectins are expressed primarily on leukocytes and 

endothelial cells. They play an important role in host 

defense mechanisms. In contrast to other CAMs, selectins 

bind to carbohydrate ligands. Hence, the resulting binding 

forces are relatively weak. This allows selectin-mediated 

interactions between leukocytes and endothelial cells and 

promotes rolling of the leukocytes along the endothelium. 

L-selectins are expressed on most leukocytes, E-selectins 

are inducible on vascular endothelium upon stimulation 

with cytokines, and P-selectins are found on activated 

platelets and vascular endothelium. 

Dysregulation of several CAMs, particularly the Ig- 

CAMs, has been linked to tumor progression and 

metastasis, making them a suitable target for therapeutic 

intervention. Also, increased expression of CAMs 

on the vascular endothelium is postulated to play an 

important role in atherogenesis. CAMs also play critical 

roles in the recruitment and migration of cells to sites 

of inflammation. Hence, these molecules have become 

targets for the development of drugs for treatment of 

cancer, inflammation, and autoimmune diseases. 

References: 

Cavallaro, U., and Christofori, G. 2004. Nat. Rev. Cancer 4, 8. 

Aplin, A.E., et al. 999. Curr. Opin. Cell Biol. 11, 737. 

Meredith, J.E., et al. 997. Trends Cell Biol. 7, 46. 

Ruoslahti, E., and Obrink, B. 996. Exp. Cell Res. 227, . 

Law, D.A., et al. 996. J. Biol. Chem. 271, 08 . 

Flores, M.E., et al. 996. Exp. Cell Res. 227, 40. 

More online... www.calbiochem.com/inhibitors/ca 


Phone 800 628 8470 


69


Cell Adhesion Inhibitors 


H-Arg-Gly-Asp-OH 03-34-0029 (Arginyl-glycyl-aspartic Acid; RGD) 

Amino acid sequence within fibronectin that mediates cell attachment. 

H-Arg-Gly-Asp-Ser-OH 03-34-0002 (Fibronectin Inhibitor; RGDS) 

Shown to inhibit fibronectin function by binding to platelet-binding sites. 

BAY -7082 196870 {(E)3-[(4-Methylphenyl)sulfonyl]-2-propenenitrile} 

Potential anti-inflammatory agent. Selectively and irreversibly inhibits the 

TNFa-inducible phosphorylation of IkBa (IC 50 = 0 mM) without affecting the 

constitutive IkBa phosphorylation. Decreases nuclear translocation of NF-kB 

and inhibits TNFa-induced surface expression of the endothelial-leukocyte cell 

adhesion molecules E-selectin, VCAM- , and ICAM- . 

BAY -7085 196872 {(E)3-[(4-t-Butylphenyl)sulfonyl]-2-propenenitrile} 

Exhibits biological properties similar to that of BAY -7082 (Cat. No. 96870). BAY 

-7085 has also been shown to have potent anti-inflammatory properties in vivo. 

Cell Sheet Migration 


Cell Sheet Migration 

Inhibitor, Negative 

Control 

Cyclo(Arg-Gly-Asp-D- 

Phe-Val) 

219469 {(4S)-3-[(E)-But-2-enoyl]-4-benzyl-2-oxazolidinone; UIC-1005 

A cell-permeable N-(crotonyl)oxazolidinone compound that acts as a potent, 

reversible inhibitor of eukaryotic cell migration and growth (IC 50 = 4 mM for 

inhibition of wound closure in MDCK cell monolayers). May serve as a useful tool 

for studying motility-related signaling pathways. 

219470 [(4S)-3-butyryl-4-benzyl-2-oxazolidinone; UIC-1017] 

A cell-permeable N-(butyryl)oxazolidinone compound that serves as a negative 

control for the Cell Sheet Migration Inhibitor (Cat. No. 2 9469). Displays little bioactivity 

in wound closure and cell proliferation studies (IC ≥ 500 mM for wound 

50 

closure in MDCK cell monolayers). 

182015 (RGDFV Peptide, Cyclic) 

Potent inhibitor of cell adhesion. Inhibits tumor cell adhesion to laminin and 

vitronectin substrates. 

FR- 05-23-1701 (CRGDSPASSC, Cyclic) 

A cyclic peptide containing the cell binding domain Arg-Gly-Asp and associated 

cell migration Pro-Ala-Ser-Ser sequences of fibronectin. A potent inhibitor of ADPinduced 

platelet aggregation (IC 50 = 7.6 mM). 

H-Gly-Arg-Ala-Asp- 

Ser-Pro-OH 

H-Gly-Arg-Gly-Asp- 

Ser-OH 


Ser-Pro-OH 


Thr-Pro-OH 

03-34-0052 (GRADSP) 

Inactive control peptide for fibronectin inhibitors. 

03-34-0027 (GRGDS) 

A cell-binding protein domain that competitively inhibits direct binding of 

fibroblasts to fibronectin. Also, reported to inhibit the migration of vascular 

smooth muscle cells into fibrin gels. 

03-34-0035 (GRGDSP) 

Shown to inhibit fibronectin binding to platelet-binding sites. 

03-34-0055 (GRGDTP) 

Inhibits binding of fibrinogen, fibronectin, vitronectin, and von Willebrand factor 

to platelets. Also inhibits cell attachment to collagen, fibronectin, and vitronectin. 

Pentoxifylline 516354 [3,7-Dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione; PTX] 

A non-selective phosphodiesterase inhibitor that inhibits the adhesion of T cells to 

the b and b 2 integrin ligands VCAM- and ICAM- . 

P-Selectin Antagonist 561308 (Galloyl-N-gaba-WVDV-OH) 

A specific, high affinity inhibitor of human P-selectin ligand (IC 50 = 5.4 nM). 

Displays weaker affinity towards mouse P-selectin, human L, and E-selectins. 

Shown to block monocyte-derived HL-60 cell adhesion to P-selectin-transfected 

CHO cells (EC 50 = 74 nM). 

25 mg $77 

25 mg $ 05 

0 mg $68 

0 mg $88 

0 mg $ 2 

5 mg $73 

mg $ 56 

mg $95 

70 Orders Phone 800 854 34 7 


Fax 800 776 0999 


5 mg 

25 mg 

$47 

$ 77 

25 mg $227 

5 mg 

25 mg 

5 mg 

25 mg 

$48 

$ 82 

$46 

$ 77 

500 mg $28 

5 mg $ 52

DNA Methyltransferase Inhibitors 

DNA methylation is one of the most prevalent epigenetic 

modifications of DNA in mammalian genomes. It is 

achieved by DNA methyltransferases that catalyze 

the addition of a methyl group from S-adenosyl- 

L-methionine to the 5-carbon position of cytosine. 

Methylation at cytosine plays an important role in 

regulating transcription and chromatin structure. 

Methylated DNA can trigger chromatin reorganization 

mediated by methyl-binding proteins. Four families 

of DNA methyltransferase genes have been identified 

in humans. They include Dnmt1, Dnmt2, and Dnmt3b, 

which encode proteins with different functional 

specificities. Dnmt1 is constitutively expressed in 

proliferating cells and its inactivation results in 

demethylation of genomic DNA and embryonic death. 

Dnmt2 is expressed at low levels in adult tissues. 

Its inactivation does not affect DNA methylation or 

maintenance of methylation. Dnmt3a and Dnmt3b are 

strongly expressed in embryonic stem cells, but are 

down-regulated in differentiating embryonic stem cells 

and in adult somatic cells. 

Most mammalian transcription factors bind GC-rich DNA 

elements, and methylation within these elements reduces 

their ability to bind. CpG methylation is shown to induce 

histone deacetylation, chromatin remodeling, and gene 

silencing through a transcription repressor complex. 

DNA Methyltransferase Inhibitors 



CpG islands are often located around the promoters of 

housekeeping genes and are not methylated. On the 

contrary, the CG sequences in inactive genes are usually 

methylated to suppress their expression. 

Aberrant DNA methylation has been linked to several 

pathological conditions. Mutations in DNA methyltransferase 

3b are known to cause ICF (immunodeficiency, 

centromere instability and facial anomalies) syndrome. 

Overexpression of DNA methyltransferases has been 

implicated in the development of several tumors. About 

25% of all mutations in the p53 gene in human cancers 

are reported to occur at CpG sites. Methylation of these 

sites can inactivate and silence tumor suppressor genes. 

Abnormal DNA methylation also occurs during aging and 

alters gene activity, thus affecting a variety of cellular 

functions. 

References: 

Stresemann, C. et al. 2006. Cancer Res. 66, 2794. 

Lee, W.J. et al. 2005. Mol. Pharmacol. 68, 0 8. 

Lyko, F., and Brown R. 2005. J. Natl. Cancer Inst. 97, 498. 

Lehmann, U., et al. 2004. Ann. Hematol. 83, 37. 

Paz, M.F., et al. 2003. Human Mol. Genetics 12, 2209. 

Robertson, K.D. 200 . Oncogene 20, 3 39. 

Xu, G.L., et al. 999. Nature 402, 87. 

Okano, M., et al. 998. Nucleic Acids Res. 28, 2536. 

Issa, J.P., et al. 993. J. Natl. Cancer Inst. 85, 235. 


5-Aza-2´-Deoxycytidine 189825 (5-Aza-CdR; 5-Aza-dC; 5-Deoxy-2´-azacytidine) 

A cytosine analog that acts as a DNA methyltransferase inhibitor. Also enhances 

apoptosis induced by histone deacetylase inhibitors. 

N DNA Methyltransferase 


(–)-Epigallocatechin 

Gallate 

More online... www.calbiochem.com/inhibitors/DNAm 

260920 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propionic acid; RG108 

A cell-permeable specific inhibitor of DNA methyltransferases (IC 50 = 5 nM for 

CpG methylase M.SssI) and displays anti-proliferative properties. Suggested to 

directly target the enzyme active sites, block DNA methylation, and re-activate 

tumor suppressor genes. 

324880 A polyphenolic compound with antitumor, anti-inflammatory, and anti-oxidant 

properties. An inhibitor of Dnmt1 (IC 50 = 2 0-470 nM). 

N InSolution Sinefungin 567051 (A9145; Adenosyl-ornithine; SF) 

A 0 mM (2 mg/524 ml) solution of Sinefungin in H 2 O. An anti-leishmanial 

nucleoside antibiotic that acts as an S-adenosyl-L-methionine (SAM, AdoMet) 

methyltransferase-specific inhibitor. 

Zebularine 691400 [2-Pyrimidone-1-b-D-riboside; 1-(b-D-Ribofuranosyl)-1,2-dihydropyrimidin-2-one] 

A chemically stable cytidine analog that displays antitumor properties. An inhibitor 

of DNA methylation and tumor growth both in vitro and in vivo. Also acts as 

transition state analog inhibitor of cytidine deaminase by binding at the active site 

as covalent hydrates. 

25 mg $ 78 

0 mg $ 24 

0 mg $39 

2 mg $ 39 

0 mg 

25 mg 

$ 2 

$258 


Phone 800 628 8470 


7


DNA and RNA Polymerase Inhibitors 

DNA polymerases build DNA by forming a 

phosphodiester bond between the 5á-phosphate of one 

deoxyribonucleotide and the 3´-hydroxyl of another. 

They cannot initiate DNA synthesis de novo, but add 

deoxynucleotides, one at a time, to the 3´-hydroxyl 

terminus of a preexisting DNA or RNA strand (a primer). 

Most DNA polymerases require a template bound to the 

primer, and extend the primers by synthesizing strands 

complementary to the template; while most prefer DNA 

templates, reverse transcriptase prefers RNA templates. 

Some DNA polymerases, such as terminal transferase, 

are template-independent. RNA polymerases build 

(transcribe) RNA strands by forming a phosphodiester 

bond between the 5á-phosphate of one ribonucleotide 

and the 3´-hydroxyl of another. DNA template-dependent 

RNA polymerases can initiate RNA strand synthesis de 

novo, yielding complementary RNA transcripts. Poly- 

A polymerase is template-independent, and adds A 

residues to the 3´-hydroxyl termini of preexisting RNA 

transcripts. Retroviruses specify reverse transcriptases, 

which are RNA-dependent DNA polymerases that reverse 

transcribe the retroviral RNA genome into DNA. 

DNA and RNA Polymerase Inhibitors 

Inhibitors of DNA and RNA polymerases are invaluable 

tools in both clinical and research settings. The use of 

DNA and RNA polymerase inhibitors aids in delineating 

the mechanistic aspects of transcription and DNA 

replication, in defining structure-function relationships, 

and in protein turnover studies. Characterizing 

mutations that can confer resistance to antibiotics 

can help identify the genomic loci that encode for the 

respective subunit of the target enzyme. As DNA and 

RNA polymerases are among the most attractive drug 

targets, the knowledge about these inhibitors, their 

structures, and their modes of action provides the basis 

for design of new drugs/antibiotics that will be effective 

against new pathogens and antibiotic-resistant mutants 

of known pathogens. Because some of these agents block 

specific steps (transcription) in the processes that lead 

from DNA to protein, their use can help delineate the role 

of transcriptional control in regulating the expression 

of target genes in health and disease. Furthermore, some 

of these inhibitors can be used in studies requiring the 

synchronization of the cell cycle; also since some have 

been reported to induce and/or inhibit apoptosis, these 

represent valuable tools for apoptosis-related studies. 


Actinomycin D, 


Actinomycin D, 7- 

Amino- 

a-Amanitin, Amanita 

sp. 

Methyl a-Amanitin 

Oleate 

114666 (Dactinomycin) 

Antineoplastic antibiotic that inhibits DNA-primed RNA polymerase by complexing 

with DNA via deoxyguanosine residues. At higher concentrations, DNA polymerase 

is inhibited. 

129935 (7-AAD; 7-Amino-AMD; 7-Aminoactinomycin C 1 ; 7-Aminodactinomycin) 

A membrane impermeable fluorescent DNA intercalator. Inhibits RNA polymerase 

far more specifically than DNA polymerase. 

129741 A potent and specific inhibitor of RNA polymerase II and mRNA synthesis in higher 

eukaryotes. 

454559 A semi-synthetic derivative of a-Amanitin, Amanita sp. (Cat. No. 2974 ) that is 

about 30-fold more cell-permeable than a-Amanitin. 

Aphidicolin 178273 A cell synchronization agent that blocks the cell cycle at the early S-phase. 

Specific inhibitor of DNA polymerase a and d in eukaryotic cells and in some 

viruses of animal origin. 

N HSV Replication 

Inhibitor, BP5 

Novobiocin, Sodium 

Salt 

385883 Disrupts the interaction between the catalytic subunit UL30 (Pol) and the 

processing subunit UL42 of herpes simplex virus DNA polymerase (IC 50 ~4 mM). 

491207 A DNA gyrase inhibitor that can be used for the production of positively 

supercoiled plasma DNA. Targets the nucleotide-binding site of gyrase B. Inhibits 

retrovirus RNA-dependent DNA polymerases. 

Rifampicin 557303 [3-(4-Methylpiperazinyliminomethyl)rifamycin SV; Rifampin] 

Antibiotic that specifically inhibits DNA-dependent bacterial RNA polymerase by 

forming an inactive complex with RNA polymerase. Does not affect mammalian 

RNA polymerase. 

RNA Polymerase III 


More online... www.calbiochem.com/inhibitors/DNARNA 

557403 {N-[1-(3-(5-Chloro-3-methylbenzo[b]thiophen-2-yl-1-methyl-1H-pyrazol-5-yl)]-2chlorobenzenesulfonamide; 

ML-60218} 

A cell-permeable broad spectrum inhibitor of RNA polymerase III (IC 50 = 27 mM and 

32 mM for human and S. cerevisiae RNA polymerase III, respectively). 

72 Orders Phone 800 854 34 7 


Fax 800 776 0999 


5 mg 

set 

$73 

$ 22 

mg $ 3 

mg $ 64 

00 mg $87 

mg $74 

0 mg $90 

g 

0 g 

g 

5 g 

$27 

$ 50 

$59 

$228 

0 mg $ 52

Histone Acetylase and Deacetylase Inhibitors 

Gene expression, to a large extent, is controlled by a host 

of protein complexes that continuously pack and unpack 

the chromosomal DNA from the inaccessible, tightly 

packed nucleosomal particles to the accessible, unwound 

nucleosomal particles. This packing and unpacking is 

achieved by the acetylation and deacetylation of the 

histones in the nucleosomal core. Acetylated histone 

proteins confer accessibility of the DNA template to 

the transcriptional machinery for expression. Histone 

acetylation has been linked to gene-specific activation 

by transcription factors. It plays an important role in 

cell cycle control and has been linked to uncontrolled 

cell proliferation. Histone deacetylases (HDAC), on the 

other hand, are chromatin-remodeling factors that act 

as transcriptional repressors or silencers of genes. 

They regulate histone acetylation by catalyzing the 

removal of acetyl groups on the amino terminal lysine 

residues of the core nucleosomal histones. In humans 

at least 16 different HDACs have been reported that 

are subdivided into Class I (HDAC 1, 2, 3, and 8); Class 

II (HDAC 4, 5, 6, 7, 9, and 10), and Class III (SIRT 1- 

7). Class I HDACs are widely expressed in tissues, 

Histone Acetylase and Deacetylase Inhibitors 



and are primarily located in the nucleus. Class II 

HDACs are much larger in size and display limited 

tissue distribution. They can shuttle between the 

nucleus and cytoplasm. Class III HDACs consist of a 

large family of sirtuins (silent information regulators 

or SIR) that are evolutionarily distinct, with unique 

enzymatic mechanisms dependent on NAD + . Studies 

have shown that certain oncogenes repress transcription 

by recruitment of HDACs. This has led to the interest 

in small molecules that act as inhibitors of HDAC and 

have potential for the treatment of cancer. They act as 

potent inducers of growth arrest, differentiation, and 

apoptotic cell death in a variety of transformed cells in 

culture and in tumor bearing animals. They are shown 

to increase the DNA-binding activities of AP1, CREB, 

and NF-kB transcription factors and are also reported to 

down-regulate telomerase activity via suppression 

of hTERT mRNA expression. The best-studied inhibitor 

of HDAC is Trichostatin A, a hydroxamic acid that 

complexes with zinc and mediates the acetamide 

cleavage at the catalytic site. 

References: 

Acharya, M. R., et al. 2005. Mol. Pharmacol. 68, 9 7. 

Mei, S. et al. 2004. Int. J. Oncol. 25, 509. 

Suenaga, M., et al. 2002. Int. J. Cancer 97, 62 . 

Marks, P.A., et al. 200 . Curr. Opin. Oncol. 13, 477. 

Yoshida, M., et al. 200 . Cancer Chemother. Pharmacol. 48 ( Suppl ):S20. 

Jung. M., et al. 200 . Curr. Med. Chem. 8, 505. 

Pandolfi, P.P., 200 . Cancer Chemother. Pharmacol. 48 (Suppl ), S 7. 

Munster, P.N., et al. 200 . Cancer Res. 61, 8492. 


Anacardic Acid 172050 (AA; 2-Hydroxy-6-pentadecylbenzoic Acid; 6-Pentadecylsalicylic Acid) 

A cell-permeable salicylic acid analog that acts as a potent, non-competitive 

inhibitor of p300 and PCAF (p300/CBP-associated factor) histone 

acetyltransferase (HAT) activities (IC 50 ~8.5 mM and ~5 mM, respectively). 

Apicidin, Fusarium sp. 178276 {cyclo-[L-(2-Amino-8-oxodecanoyl)-L-(N-methoxytryptophan)-L-isoleucyl-Dpipecolinyl]} 

Histone Deacetylase 


More online... www.calbiochem.com/inhibitors/HAD 

A potent, cell-permeable inhibitor of histone deacetylase (IC 50 = 700 pM for 

parasitic histone deactetylase). 

382147 {N-(2-Aminophenyl)-4-[N-(pyridine-3-ylmethoxycarbonyl)aminomethyl]benzamide; 

MS-275} 

A benzamide analog that acts as a histone deacetylase inhibitor (IC 50 = 2.0 mM) 

and exhibits anti-tumor properties. Suitable for use in both in vitro and in vivo 

applications. 

0 mg $79 

mg 

5 mg 

mg 

5 mg 

$87 

$226 

$52 

$ 74 


Phone 800 628 8470 


73


Histone Acetylase and Deacetylase Inhibitors, continued 


Histone Deacetylase 382148 (m-Carboxycinnamic Acid bis-Hydroxamide; CBHA) 

5 mg — 


A second-generation hybrid polar agent that has been shown to inhibit the 

activities of histone deacetylase (HDAC) and 3 (ID = 0 nM and 7 nM, 

50 

respectively) in MEL DS 9/Sc9 cells. The HDAC inhibition is believed to arise as a 

result of the binding of the hydroxamic moiety to the active site zinc. Not available 

for sale in the United States. 

Histone Deacetylase 382149 [4-Dimethylamino-N-(6-hydroxycarbamoylhexyl)benzamide; N-Hydroxy-7-(4-dimethy mg $93 


laminobenzoyl)aminoheptanamide; M344] 

An amide analog of Trichostatin A (Cat. No. 647925) that potently inhibits histone 

deacetylase (IC = 40 nM for rat liver HDAC and IC = 00 nM for maize HDAC). 

50 50 

5 mg $284 

ITSA 419840 [N-(1H-Benzotriazol-1-yl)-2,4-dichlorobenzamide; Inhibitor of Trichostatin A 1] 

A cell-permeable benzotriazole amide that can be used to counteract Trichostatin 

A-induced cell cycle arrest, histone acetylation, and transcription activation. 

25 mg $79 

mg $87 

5 mg $297 

Oxamflatin 499700 {(2E)-5-[3-(Phenylsulfonylamino)phenyl]pent-2-en-4-ynohydroxamic Acid} 

An aromatic sulfonamide derivative with a hydroxamic acid group that potently 

inhibits mammalian histone deacetylase (IC 50 = 5.7 nM). Acts as a ligand for the 

enzyme active site metal ion. 

SBHA 559418 (Suberic Bishydroxamate; Suberoyl Bishydroxamic Acid) 

A histone deacetylase (HDAC) inhibitor with anti-tumor properties. Reported to 

cause an increase in acetylated histone H4 in MEL cells. Also reported to inhibit 

human HDAC and HDAC3 activities with a similar potency (ID ~250–300 nM). 

50 

Not available for sale in the United States. 

Scriptaid 565730 {CGK1026; 6-(1,3-Dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-hexanoic Acid 

Hydroxyamide 

A relatively non-toxic hydroxamic acid-containing histone deacetylase (HDAC) 

inhibitor. Causes over 00-fold increase in histone acetylation in PANC- cells at 

6 mM. 

Sirtinol 566320 {2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide; Sir Two 

Inhibitor Naphthol} 

A cell-permeable, specific, and a direct inhibitor of the sirtuin class of histone 

deacetylase (HDAC) activity. Does not affect human HDAC . Reported to block 

Sir2p transcriptional silencing activity in vivo (IC = 25 mM) and NAD-dependent 

50 

HDAC activity in purified recombinant yeast Sir2p and human SIRT2 in vitro 

(IC = 68 mM and 38 mM, respectively). 

50 

N InSolution Sirtinol 566321 {2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide; Sir Two 

Inhibitor Naphthol} 

A 0 mM ( mg/254 ml) solution of Sirtinol (Cat. No. 566320) in DMSO. 

Splitomicin 567750 (1,2-Dihydro-3H-naphtho[2,1-b]pyran-3-one) 

A cell-permeable, selective inhibitor of NAD + -dependent histone deacetylase 

activity of Sir2 protein (IC = 60 mM). It creates a conditional phenocopy of a Sir2 

50 

deletion mutant in S. cerevisiae and sensitizes mammalian cells to a variety of 

DNA-damaging agents by abrogating Sir2p activity on p53. Acts by either altering 

or blocking access to the acetylated histone binding pocket. 

Trichostatin A, 


N InSolution Trichostatin 

A, Streptomyces sp. 

Valproic Acid, Sodium 

Salt 

647925 (4,6-Dimethyl-7-[p-dimethylaminophenyl]-7-oxahepta-2,4-dienohydroxamic Acid; TSA) 

A potent and reversible inhibitor of histone deacetylase. 

647926 A 0 mM (500 mg/ 65 ml) solution of Trichostatin A, Streptomyces sp. 


676380 (2-Propylpentanoic Acid, Na) 

A cell-permeable, short-chain fatty acid that inhibits histone deacetylase 

(IC = 400 mM for HDAC ). Induces differentiation and inhibits proliferation 

50 

of cell lines derived from human malignant gliomas. 

00 mg — 

5 mg $96 

5 mg $ 6 

mg $58 

5 mg $ 03 

mg $ 56 

500 mg $90 

5 g $48 

74 Orders Phone 800 854 34 7 


Fax 800 776 0999 



Histone Deacetylase Activity Assay Kit, 

Colorimetric 

A rapid, two-step assay that measures histone deacetylase (HDAC) 

activity in cell lysates. Deacetylation by HDAC results in a sensitized 

substrate that, when treated with the lysine developer, produces 

a chromophore that can be measured at 400 or 405 nm by a 

spectrophotometer or a plate reader. kit = 00 assays 

Cat. No. 382166 1 kit $372 

N Histone Deacetylase, Human, Recombinant, 

S. frugiperda 

Recombinant human histone deacetylase 3 (HDAC3) expressed in 

insect cells using a baculovirus expression system. HDAC3 is a class I 

histone deacetylase that regulates gene expression by deacetylation 

of histones and nonhistone proteins. It is suggested that HDACs play 

an important role in transcriptional regulation, cell cycle progression 

and activation, and biological processes in eukaryotes that involve 

chromatin. 

Cat. No. 382169 5000 U $345 

Histone Deacetylase, Rat Liver 

An enzymatically active, partially purified, histone deacetylase 

from rat liver. Useful in radioactive and in nonradioactive assays of 

histones. Can be useful to test the potency of HDAC inhibitors. 

Cat. No. 382165 2 ml $284 




Fluorometric 

A rapid, two-step assay that measures histone deacetylase (HDAC) 

activity in cell lysates. Deacetylation by HDAC results in a sensitized 

substrate that, when treated with the lysine developer, produces a 

fluorophore that can be measured at 440-460 nm by a fluorometer or 

a fluorescence plate reader. kit = 00 assays 

Cat. No. 382167 1 kit $350 

Histone Deacetylase HD2, Maize 

An enzymatically active, highly purified, histone deacetylase (HDAC) 

from maize embryos. Shown to be useful for screening of HDAC 

Inhibitors (IC 50 = 7.2 nM for TSA, 0 nM for Trapoxin, 50 nM for SAHA, 

and 0 nM for HC-Toxin). Reported to be a multimer-protein complex 

that dissociates into three polypeptides (p39, p42, and p45) upon 

denaturation. 

Cat. No. 382168 500 ml $303 

To download free Interactive Pathways screensavers 

visit us at www.calbiochem.com/screensavers 


Phone 800 628 8470 


75


Nuclear Import/Export Inhibitors 

Proteins required for nuclear functions are specifically 

transported from the cytoplasm into the nucleus. 

In general, proteins larger than 25 nm in diameter 

(~30 kDa) can only enter the nucleus in an energydependent 

process, which calls for the participation of 

a variety of soluble import factors. Trafficking between 

the nucleus and the cytoplasm occurs via the nuclear 

pore complexes (NPCs). NPCs are large supramolecular 

assemblies of ~125 MDa and contain about 100 

polypeptides embedded in the double-membrane nuclear 

envelope. The NPCs allow passive diffusion of ions and 

small molecules, whereas nuclear proteins, RNAs, and 

ribonucleoproteins larger than ~9 nm in diameter are 

selectively and actively transported by a signal-mediated 

and energy-dependent mechanism. The signal for import 

is provided by a peptide sequence in the encoded protein 

known as the nuclear localization signal (NLS). 

The presence of several different NLSs and import 

factors suggests the existence of multiple pathways 

for such an import. 

A number of nuclear transport receptors known as 

importins (karyopherins), transportins, and Ran-binding 

proteins recognize the NLS and mediate “docking” at the 

nuclear pore. Importin-a (karyopherin-a), the cytoplasmic 

receptor for NLS-bearing proteins, binds importin-b via 

a specific binding domain. Importin-b interacts with the 

importin-a bound to the NLS and acts as a carrier of the 

NLS/importin-a/b trimer. This trimeric complex docks 

to the cytoplasmic filaments of the NPC via importin-b. 

Subsequent passage of import substrates from the NPC into 

the nuclear interior requires the small GTPase, Ran, which 

plays a crucial role in both import/export pathways and 

determines the directionality of nuclear transport. Once 

in the nucleus, importin-b binds RanGTP and the import 

complex is disassembled and the substrate is retained in 

Nuclear Import/Export Inhibitors 

the nucleus. Ran is reported to shuttle between the nucleus 

and the cytoplasm. Recycling of Ran is essential for nuclear 

transport. In the cytoplasm, Ran is maintained primarily in 

its GDP-bound form to facilitate import. On the other hand, 

in the nucleus, Ran is bound to GTP through RCC1, which 

facilitates export of proteins. 

Malfunctioning of the nucleo-cytoplasmic transport is 

profoundly involved in a number of diseases. Defects 

in NPC components have been implicated in several 

autoimmune disorders and cancers. At least 11 chromosomal 

rearrangements in acute leukemia involve nuclear pore 

protein (nucleoporin) genes. Leukemias associated with 

nucleoporin gene rearrangements have been reported to be 

more refractory to therapeutic intervention. 

References: 

Menendez, S., et al. 2003. Br. J. Cancer 88, 636. 

Weis, K. 2003. Cell 112, 44 . 

Kroon, E., et al. 200 . EMBO J. 20, 350. 

Arai, Y., et al. 2000. Leukemia 14, 62 . 

Barry, D.M., and Wente, S.R. 2000. Essays Biochem. 36, 89. 

Fontoura, B. M. A., 2000. J. Biol. Chem. 275, 3 289. 

Talcott, B., and Moore, M.S. 2000. J. Biol. Chem. 275, 0099. 

Nakielny, S., and Dreyfuss, G. 999. Cell 99, 677. 

Stoffler, D., et al. 999. Curr. Opin. Cell Biol. 11, 39 

Kutay, U., et al. 997. Cell 90, 06 . 

Gorlich, D., et al. 995. Nature 377, 246. 

More online... www.calbiochem.com/inhibitors/nuclear 


InSolution Leptomycin 431051 (ATS1287 A; LMA) 

mg $ 52 

A, Streptomyces sp. 

Supplied as a mg/200 ml solution in 70% methanol. An antifungal antibiotic 

that acts as an inhibitor of nuclear export. Shown to inhibit nucleo-cytoplasmic 

translocation of human immunodeficiency virus type regulatory protein (Rev) at 

nanomolar concentrations. 

InSolution Leptomycin 431050 (LMB) 

mg $3 3 

B, Streptomyces sp. 

Supplied as a 5 mg/ml ( mg/200 ml) solution in 70% methanol. A potent inhibitor 

of CRM -mediated (exportin- ) nuclear export. Shown to inhibit nucleocytoplasmic 

translocation of human immunodeficiency virus type regulatory 

protein (Rev) at nanomolar concentrations and block Rev-dependent export of 

mRNA into the cytoplasm. Useful for studies involving nuclear localization and 

protein trafficking in eukaryotic cells. 

76 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Nuclear Import/Export Inhibitors, continued 




InSolution Ratjadone 553590 Supplied as a 5 mg/ml (2 mg/400 ml) solution in methanol. A cell-permeable 

2 mg $ 95 

A, Synthetic 

polyketide with antitumor properties. Originally identified as a metabolite from 

the myxobacterium Sorangium cellulosum for its antibiotic activities against 

yeasts and filamentous fungi, ratjadones inhibit nuclear export of LR-NES (leucine 

rich-nuclear export signal)-containing proteins by covalently binding to CRM 

(Chromosome region maintenance ). 

Nuclease Inhibitors 


Aurintricarboxylic Acid 189400 A cell-permeable, polyanionic, polyaromatic compound used as a powerful 

inhibitor of cellular processes that are dependent on the formation of proteinnucleic 

acid complexes. Binds to acidic fibroblast growth factor (aFGF) and reduces 

its angiogenic activity. Shown to inhibit apoptotic cell death in various cell types 

induced by a variety of factors. ATA is a potent inhibitor of DNA topoisomerase II 

(IC = 75 nM for the yeast enzyme as measured by relaxation assays) that also acts 

50 

as a potent inhibitor of angiogenesis. Stimulates the tyrosine phosphorylation of 

MAP kinases, Shc proteins, phosphatidylinositol 3-kinase, and phospholipase Cg. 

Inhibits both major calpain isoforms (IC = 22 mM and IC = 0 mM for m-calpain 

50 50 

and m-calpain, respectively). 

00 mg $34 

Diethyl Pyrocarbonate 298711 DEPC, Diethyl Oxydiformate 

Useful for specific inactivation of nucleases during isolation of undegraded 

polynucleotides. 

N DNA Base Excision 

Repair Pathway 


DNase g Inhibitor, 

6-DTAF 

Ribonuclease Inhibitor, 

Human Placenta 

Ribonuclease Inhibitor, 

Human, Recombinant, 

E. coli 

262015 [7-Nitroindole-2-carboxylic acid] 

A cell-permeable, potent, specific, and nontoxic inhibitor of the DNA repair 

enzyme, APE (human apurinic/apyrimidinic endonuclease; IC 50 ~3 mM). Shown 

to target the APE active site and inhibit its 3'-phosphodiesterase and 3'phosphatase 

activities. Exhibits minimal effects on endonuclease IV, BamHI 

restriction endonuclease, or topoisomerase I at 00 mM. Also shown to potentiate 

the cytotoxicity of several DNA damaging agents, such as MMS, temozolomide, 

Zeocin, and H 2 O 2 in HeLa, HT 080, and MDA-MB-23 cells. 

260905 4-(4,6-Dichloro-[1,3,5]-triazin-2-ylamino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic 

acid; 6-(4,6-Dichlorotriazinyl)aminofluorescein; DR396 

A potent and selective inhibitor of DNase g, human (IC = 3.2 mM). 

50 

556883 A tight-binding potent inhibitor of pancreatic ribonuclease and angiogenin. Plays 

an important role in the control of mRNA degradation and gene expression. 

Consists of seven leucine-rich internal repeats, each with 57 amino acid residues. 

The molecular weight, immunoreactivity and amino acid composition of rhPRI are 

identical to those of native PRI. 

556881 Non-competitive inhibitor that inactivates RNase by non-covalent binding. Has 

been used to improve cDNA synthesis and in vitro RNA synthesis, increase yields of 

polysomes, and aid in the preparation of RNase-free antibodies. Inhibits RNases A, 

B, and C. Does not inhibit RNase T and S nuclease from Aspergillus. 

25 g 

00 g 

$76 

$273 

25 mg $77 

0 mg $90 

2500 U $89 

2500 U $ 08 


Phone 800 628 8470 


77


Poly(ADP-ribose) Polymerase (PARP) and Poly(ADP-ribose) 

Glycohydrolase (PARG) Inhibitors 

Poly(ADP-ribosyl)ation (pADPr) is a covalent posttranslational 

modification process that occurs during 

DNA repair, replication, and transcription. It is brought 

about by poly(ADP-ribose)polymerases (PARP), which are 

activated by breaks in DNA strands. PARPs are a group 

of Zn 2+ -binding multi-functional enzymes that catalyze 

the transfer of ADP-ribose (ADPr) units onto protein 

acceptors to produce linear and/or branched polymers 

of ADPr. Upon binding to DNA strand breaks, activated 

PARP cleaves NAD + into nicotinamide and ADP-ribose 

and polymerizes ADP-ribose onto nuclear acceptor 

proteins, such as histones and transcription factors. 

The “classical” 113 kDa type I PARP is the major 

contributor of the poly(ADP-ribosyl)ating activity in 

higher eukaryotes. Type II PARP is smaller than the 

classical zinc-finger-containing PARP and is believed to 

participate in DNA repair during apoptosis. Type III PARP 

is a large protein containing ankyrin repeats and a PARP 

catalytic domain. 

PARP consists of three domains: a DNA-binding domain 

(DBD), an automodification domain, and a catalytic 

domain. The DBD, a 42 kDa N-terminal region, extends 

from the initiator Met to Thr 373 in human PARP. It 

contains two zinc fingers and two helix-turn-helix motifs 

and is rich in basic residues, which are involved in the 

interaction of the enzyme with DNA. The automodi- 

fication domain located in the central region, resides 

between Ala 374 and Leu 525 in human PARP. A BRCT 

(BRCA1 C-terminus) domain that lies between Ala 384 

and Ser 479 and consists of about 95 amino acids is found 

in several proteins that regulate cell-cycle checkpoints 

and DNA repair. BRCT domains are protein-protein 

interaction modules that allow BRCT-motif-containing 

proteins to establish strong and specific associations. The 

C-terminal catalytic domain, a 55 kDa segment, spans 

residues Thr 526 to Trp 1014 in human PARP. The catalytic 

activity of this fragment is not stimulated by DNA 

strand breaks. It corresponds only to the basal activity 

of the native enzyme. The ADPr transferase activity 

has been confined to a 40 kDa region at the extreme 

C-terminus of the enzyme, which is referred to as the 

minimal catalytic domain. This region can catalyze the 

initiation, elongation, and branching of ADPr polymers 

independently of the presence of DNA. The deletion of the 

last 45 amino acids at the C-terminal end of this domain 

completely abolishes enzyme activity. Residues spanning 

positions Leu 859 to Tyr 908 in human PARP are well 

conserved and comprise the “PARP signature” sequence. 

The extent of poly(ADP-ribosyl)ation is an important 

determinant of NAD + levels in cells. In normal, 

undamaged cells, NAD + levels range from 400 to 

500 mM. However, PARP activation following DNA 

damage by radiation or cytotoxic agents reduces NAD + 

levels to about 100 mM within about 15 minutes. It 

is believed that during its automodification PARP 

becomes more charged, since each residue of ADPr 

adds two negative charges on to the molecule. This 

establishes an electro-repulsive gradient between 

the polymers of ADPr which are covalently linked to 

the enzyme and DNA. When the charge becomes too 

negative, the reaction reaches a “point of repulsion” 

and the interaction between PARP and DNA is lost. The 

poly(ADP-ribosyl)ated PARP molecule is consequently 

freed from the DNA strand break and its catalytic 

activity is abolished. Subsequently, poly(ADP-ribose) 

glycohydrolase (PARG) hydrolyses the polymers present 

on PARP, thereby allowing it to resume a new cycle 

of automodification in response to DNA damage. The 

presence of PARG during PARP automodification restores 

both its affinity for DNA and its catalytic activity. 

DNA damage, the single most important factor in the 

regulation of pADPr reactions, can stimulate the catalytic 

activity of PARP by about 500-fold. Inhibition of PARP 

is shown to reduce DNA repair, increase the cytotoxicity 

of DNA-damaging agents, and enhance apoptosis. The 

cytotoxicity of PARP inhibitors is due to an increase in the 

half-life of DNA strand break, which increases genomic 

instability. PARP cleavage by caspase-3 is considered as an 

early event in apoptotic cell death. PARP degradation has 

also been reported during necrosis, although believed to be 

through a different process. 

References: 

Masutani, M., et al. 2003. Genes Chromosomes Cancer 38, 339. 

Chiarugi, A. 2002. Trends Pharmacol. Sci. 23, 22. 

Virag. L., and Szabo, C. 2002. Pharmacol. Rev. 54, 375. 

Burkle, A. 200 . BioEssays 23, 795. 

Davidovic, L. 200 . Exp. Cell Res. 268, 7. 

Tong, W.M., et al. 200 . Biochim. Biophys. Acta 1552, 27. 

DíAmours, D., et al. 999. Biochem. J. 342, 249. 

Shieh, W.M., et al. 998. J. Biol. Chem. 273, 30069. 

Mazen, A., et al. 989. Nucleic Acids Res. 17, 4689. 

Alkhatib, H.M.., et al. 987. Proc. Natl. Acad. Sci. USA 84, 224. 

More online... www.calbiochem.com/inhibitors/PARP 

78 Orders Phone 800 854 34 7 


Fax 800 776 0999 




Poly(ADP-ribose) Polymerase (PARP) and Poly(ADP-ribose) Glycohydrolase (PARG) Inhibitors 


ADP-HPD, Dihydrate, 

Ammonium Salt 

3-Aminobenzamide 165350 (3-ABA) 

4-Amino- ,8naphthalimide 

5-Aminoisoquinolinone, 

Hydrochloride 

118415 [Adenosine 5´-diphosphate (Hydroxymethyl)pyrrolidinediol, NH 4 ] 

An amino analog of ADP-ribose that acts as a highly potent, noncompetitive, and 

specific inhibitor of PARG (IC 50 = 20 nM) vs. ADP-ribose (IC 50 = 20 mM). 

An inhibitor of PARP that has minimal effect on bacterial toxin-mediated 

ADP-ribosylation. 

164585 (4-ANI) 

A potent inhibitor of poly(ADP-ribose) polymerase (PARP) (IC 50 = 80 nM) 

that significantly potentiates the cytotoxicity effects of g-irradiation. 

164300 [5-AIQ, HCl; 5-Aminoisoquinolin-1(2H)-one, HCl] 

A cell-permeable, water-soluble analog of isoquinoline that acts as a potent and 

specific inhibitor of PARP (IC 50 = 240 nM for PARP isolated from calf thymus). 

Reported to inhibit hydrogen peroxide-induced PARP activity in human cardiac 

myoblasts (Girardi cells) (IC 50 ~ 0 mM). 

DPQ 300270 {3,4-Dihydro-5[4-(1-piperindinyl)butoxy]-1(2H)-isoquinoline} 

A very potent and selective poly(ADP-ribose)polymerase (PARP) inhibitor 

(IC 50 = 40 nM). 

EB-47 324473 A cell-permeable, adenosine-substituted, isoindolinone compound that acts as a 

potent inhibitor of PARP- (IC 50 = 45 nM). 

5-Iodo-6-amino- ,2benzopyrone 

407850 (INH 2 BP) 

A lipophilic PARP inhibitor that offers protection against peroxynitrite and 

hydroxyl radicals in vitro and in vivo. Abrogates peroxynitrite-induced mitochodrial 

transmembrane potential (Dy m ) reduction. 

,5-Isoquinolinediol 419800 [1,5-Dihydroxyisoquinoline; 5-Hydroxy-1(2H)-isoquinoline] 

A potent inhibitor of poly(ADP-ribose) polymerase (PARP; IC = 390 nM). 

50 

NU 025 493800 (8-Hydroxy-2-methylquinazoline-4-one) 

A potent inhibitor of PARP (IC = 400 nM) that potentiates the cytotoxicity of 

50 

various DNA-active agents, including the DNA-methylating compound MTIC, the 

DNA strand break-inducing drug temozolomide, topotecan, bleomycin, and ionizing 

radiation in murine L 2 0 leukemia cells, Chinese hamster ovary cells, and in a 

variety of human tumor cell lines. 

PJ34 528150 A potent anti-inflammatory agent and an inhibitor of PARP (EC 50 = 20 nM). 

Shown to be about 0,000-fold more potent than the prototypical PARP inhibitor, 

3-Aminobenzamide (Cat. No. 65350) (EC 50 = 200 mM). 

TIQ-A 612100 (4H-Thieno[2,3-c]isoquinolin-5-one) 

A cell-permeable, potent inhibitor of PARP (IC 50 = 450 nM for bovine recombinant 

PARP- ). 


PARP Inhibitor Set 

Provided as a 5 vial set. Each set contains 00 mg of 3-Aminobenzamide 

(Cat. No. 65350) and 5 mg each of 5-Iodo-6-amino- ,2-benzopyrone 

(Cat. No. 407850), ,5-Isoquinolinediol (Cat. No. 4 9800), and NU 025 

(Cat. No. 493800), and mg of DPQ (Cat. No. 300270). 

Cat. No. 528820 1 set $293 

PARP Cleavage Detection Kit 

60 mg 

set 

$496 

$ 36 

00 mg $35 

00 mg $48 

mg 

5 mg 

$52 

$ 64 

mg $76 

mg $73 

5 mg $57 

5 mg $62 

5 mg $ 27 

mg 

5 mg 

$55 

$ 69 

mg $79 

An assay kit designed to detect poly(ADP-ribose) polymerase (PARP) 

cleavage by Western blotting. During apoptosis, PARP is cleaved by 

caspase-3. Cleavage of PARP from the native 6 kDa to 85 kDa is a 

hallmark of apoptosis. Each kit is provided with a highly specific rabbit 

polyclonal antibody that detects 6 kDa PARP and the 85 kDa apoptosisrelated 

cleavage fragment from human, bovine, rat, and mouse. 

Cat. No. 512729 1 kit $273 


Phone 800 628 8470 


79


Telomerase Inhibitors 

Telomerase is a specialized ribonucleoprotein composed 

of a catalytic subunit telomerase reverse transcriptase 

(TERT), and two other subunits known as telomerase 

associated protein 1 (TP1), and a ~445-nucleotide long 

telomerase RNA component (TR). Telomerase stabilizes 

telomere lengths by adding hexameric (TTAGGG) repeats 

to the ends of chromosomes, thereby circumventing 

the cumulative damage that normally occurs during 

mitotic cell division. Telomerase recognizes the G-rich 

strand of an existing telomere repeat sequence and 

elongates it in the 5´-to-3´ direction. Progressive loss of 

telomeres, a key feature of normal cells, is considered to 

be a major regulator of cellular senescence. Tumor cells 

overcome this problem by overexpressing telomerase. 

As cancer cells divide more often, on an average, they 

possess shorter telomeres than normal cells. Hence, 

without an active telomerase to maintain telomere 

length, cancer cells could reach critically short telomere 

at a faster pace than normal cells. Telomerase activity, 

which is practically undetectable in normal cells, is 

detected in the majority of tumor cells. The presence 

of telomerase activity is correlated with poor clinical 

outcome in cancer patients. Hence, telomerase inhibitors 

Telomerase Inhibitors 

are considered as potential therapeutic agents for the 

management of tumor progression. 

Promising approaches for telomerase inhibition include 

the use of mutant dominant/negative versions of human 

TERT (hTERT) and the use of antisense oligonucleotides 

directed against the template RNA component (hTR) of 

the telomerase holoenzyme. These telomerase inhibitors 

reduce telomerase activity and lead to progressive 

shortening of telomeres with each cell division, 

ultimately causing cells to undergo apoptosis. 

References: 

Altshuler, M.L., et al. 2003. Biochemistry (Mosc). 68, 275. 

Mokbel, K. 2003. Curr. Med. Res. Opin. 19, 470. 

Wu, X., et al. 2003. J. Natl. Cancer Inst. 95, 2 . 

Gomez, D., et al. 2002. Cancer Res. 62, 3365. 

Shay, J.W., et al. 200 . Hum. Mol. Gen. 10, 677. 

Rahat, M.A., et al. 999. Cancer 85, 9 9. 

Roos, G., et al. 998. Int. J. Cancer 79, 343. 

Wen, J., et al. 998. Mol. Diagn. 3, 29. 

Kim, N.W. 997. Eur. J. Cancer 33, 78 . 

Shay, J.W. 997. J. Cell. Physiol. 173, 266. 

Harrington, L., et al. 997. Science 275, 973. 


3´-Azido-3´- 

deoxythymidine 

InSolution AZT, 

Triphosphate, 

Tetralithium Salt 

3´-Deoxy-2´,3´- 

didehydrothymidine 

Ellipticine, 9-Hydroxy-, 

Hydrochloride 

(–)-Epigallocatechin 

Gallate 

More online... www.calbiochem.com/inhibitors/telomerase 

194348 (AZT) 

Inhibitor of HIV- reverse transcriptase that blocks the incorporation of 

nucleotides into newly synthesized DNA. Causes irreversible telomere shortening. 

194950 (AZTTP) 

A reverse transcriptase inhibitor that acts by docking to the active site of HIVreverse 

transcriptase. Also reported to inhibit telomerase activity in vitro 

(IC 50 = 30 mM). 

257920 A reverse transcriptase inhibitor that causes a consistent and rapid telomere 

shortening in vegetatively growing Tetrahymena. 

324680 (9-HE, HCl) 

An antitumor alkaloid that is reported to inhibit telomerase activity in cultured 

pancreatic cancer cells, in a time- and concentration-dependent manner, 

possibly through inhibition of protein kinases. It also acts as a potent inhibitor of 

topoisomerase II (IC 50 = 3.3 mM). 

324880 {EGCG; (2R,3R)-2-(3,4,5-Trihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7triol-3-(3,4,5-trihydroxybenzoate)} 

A polyphenolic constituent of green tea with potent antitumor, anti-inflammatory, 

and antioxidant properties. Strongly and directly inhibits telomerase activity in 

cell-free systems and in cancer cell lines. 

PIPER 528120 {N,N´-bis[2-(1-Piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic Diimide; Telomerase 

Inhibitor IV} 

A perylene-based ligand that potently inhibits human telomerase activity by 

binding to G-quadruplex DNA. The strongest binding site for PIPER appears to be 

the 3'-boundary of the G-quadruplex. Can also bind non-specifically to nucleic 

acids. 

0 mg $39 

mmol $ 60 

25 mg $76 

0 mg $55 

0 mg $39 

0 mg $85 

80 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Telomerase Inhibitors, continued 




Telomerase Inhibitor III, 

Sodium Salt 

Telomerase Inhibitor 

III, Negative Control, 

Sodium Salt 

Telomerase Inhibitor VI, 

Sodium Salt 

581004 [5´-d(TTAGGG)-3´; TAG-6] 

A short hexameric phosphorothioate oligonucleotide (PS-ODN) telomere mimic 

that inhibits telomerase activity in cell lysates and lengthens cell doubling time in 

vitro and in vivo at concentrations less than 2.5 mM. 

581007 [5´-d(TGTGAG)-3´] 

A control containing scrambled sequence of the short hexameric phosphorothioate 

oligonucleotide PS-ODN (Cat. No. 58 004). Useful as a control in experiments to 

show the specificity of PS-ODN-mediated biological effects. 

581006 (5´-CAGUUAGGGUUAG-3´; 2´-O-MeRNA) 

A 3-nucleotide 2'-O-MeRNA possessing terminal phosphorothioate linkages. 

Potently inhibits telomerase activity (IC 50 = 2 nM at 23˚C and 3 nM at 37˚C). 

Telomerase Inhibitor IX 581011 [N,N´-bis(2,3-Dihydroxybenzoyl)-1,3-phenylenediamine; MST-312] 

A cell-permeable, potent, and reversible inhibitor of telomerase activity 

(IC = 670 nM, TRAP lysate prepared from U937 cells). Prolonged treatment with 

50 

MST-3 2 has been reported to result in telomere shortening and growth arrest in 

U937 cells. Does not inhibit the activity of Taq DNA polymerase (IC > 3 mM). 

50 

TMPyP4 613560 [meso-5,10,15,20-Tetrakis-(N-methyl-4-pyridyl)porphine, Tetratosylate] 

A potent inhibitor of human telomerase (IC = 6.5 mM). TMPyP4 binds strongly 

50 

to DNA quadruplexes by stacking on the G-tetrads at the core of the quadruplex, 

resulting in telomerase inhibition. Fluoresces highly in the presence of quadruplex 

DNA. 

To view our collection of telomerase-related antibodies, 

visit our antibody resource 

www.calbiochem.com/antibodyresource 

50 nmol $75 

50 nmol $76 

00 nmol $ 53 

0 mg $ 03 

25 mg $73 


Phone 800 628 8470 


8


Topoisomerase Related Inhibitors 

DNA topoisomerases are nuclear enzymes that regulate 

the conformational changes in DNA topology by 

catalyzing the breakage and rejoining of DNA strands 

during the normal cell cycle. They relieve torsional 

stress during replication and transcription. The catalytic 

cycle of the enzyme consists of DNA cleavage to form a 

covalent enzyme-DNA intermediate, DNA relaxation, 

and re-ligation of the phosphate backbone to restore 

the continuity of the DNA. Three different types of 

topoisomerases have been reported in humans; Type I 

(91-kDa monomer), Type IIa (170-kDa dimer), and Type 

IIb (180-kDa dimer). Simpler organisms possess only 

topoisomerase I; however, higher organisms have all 

three types of topoisomerases. While topoisomerase 

IIa is present in all eukaryotes, IIb is present only in 

vertebrates and appears to be closely associated with cell 

differentiation, but not proliferation. Topoisomerases 

act by catalyzing the breakdown and rejoining reactions 

in the phosphodiester backbone of DNA. Topoisomerase 

I reversibly cleaves a single strand in duplex DNA 

molecule, whereas topoisomerase II breaks and rejoins 

both DNA strands. 

During the past few years topoisomerases have 

become important chemotherapeutic targets for 

cancer treatment. Several novel compounds have been 

Topoisomerase Related Inhibitors 

developed that can target either topoisomerase I or 

topoisomerase IIa-/IIb- isoforms, or all three types 

of topoisomerases. Inhibition of topoisomerase II is 

considered to be more challenging due to the complexity 

of interactions. Most inhibitors of topoisomerase II 

block the ligation step, leading to stabilized “cleavable 

complexes” between DNA and the enzyme. Most enzyme 

inhibitors function by docking into the enzyme active 

site or nearby allosteric site to block the reaction of 

the normal substrate. Inhibition of topoisomerase II 

involves two parts: the aromatic part of the inhibitor 

molecule intercalates between DNA base pairs and 

another more polar portion interacts with topoisomerase. 

Because topoisomerase II inhibitors (e.g., doxorubicin 

and etoposide) act as poisons rather than as classical 

competitive inhibitors, their action is dependent upon the 

level of the enzyme in cells. Rapidly proliferating cells, 

which contain relatively higher levels of topoisomerase II, 

appear to be more sensitive to these agents. 

References: 

Leppard, J. B., and Champoux, J. J. 2005. Chromosoma 114, 75. 

Topcu, Z. 200 . J. Clin. Pharm. Ther. 26, 405. 

Felix, C.A. 200 . Med. Pediatr. Oncol. 36, 525. 

Bakshi, R.P., et al. 200 . Crit. Rev. Biochem. Mol. Biol. 36, . 

Champoux, J.J. 2000. Ann. N. Y. Acad. Sci. 922, 56. 

Fortune, J.M., and Osheroff, N. 2000. Prog. Nucleic Acid Res. Mol. Biol. 64, 22 . 


N Acetyl- -keto-b- 

Boswellic Acid, 

Boswellia serrata 

110123 (3-O-Acetyl-11-keto-b-Boswellic Acid; AKBA; AKbBA) 

Reported to inhibit calf thymus topoisomerase I ( ≥ 0 mM). 

AG 387 658520 [AG 555, 5-Iodo; a-Cyano-(3,4-dihydroxy)-5-iodo-N-(3-phenylpropyl)cinnamide; 2- 

Cyano-3-(3,4-dihydroxy-5-iodo-phenyl)-N-(3-phenylpropyl)acrylamide] 

Aurintricarboxylic Acid 189400 (ATA) 

Camptothecin, 

Camptotheca 

acuminata 

Camptothecin, 0- 

Hydroxy-, Camptotheca 

acuminata 

Daunorubicin, 

Hydrochloride 

An analog of tyrphostin AG 555 (Cat. No. 658404) that acts as an inhibitor of EGFR 

tyrosine kinase and of DNA topoisomerase I. 

A polyanionic, polyaromatic compound that inhibits apoptotic cell death in various 

cell types induced by a variety of factors. A potent inhibitor of DNA topoisomerase II. 

208925 {4-Ethyl-4-hydroxy-1H-pyrano[3´,4´:6,7]indolizino[1,2-b]quinoline- 

3,14(4H,12H)dione} 

More online... www.calbiochem.com/inhibitors/topoisomerase 

A reversible DNA topoisomerase I inhibitor that binds to and stabilizes the 

topoisomerase-DNA covalent complex. 

390238 (HCPT; 10-Hydroxycamptothecin) 

A powerful DNA topoisomerase I inhibitor that reduces DNA synthesis in murine 

hepatoma cells. Has a selective inhibitory effect on the phosphorylation of 

histones H and H3, but is less effective on other histones. 

251800 (Daunomycin, HCl) 

Potent anticancer agent that inhibits RNA and DNA synthesis by intercalating into 

DNA. Inhibits eukaryotic topoisomerase I and II. 

5 mg $ 68 

5 mg $87 

00 mg $34 

50 mg $62 

25 mg $92 

5 mg $6 

82 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Topoisomerase Related Inhibitors, continued 




Doxorubicin, 

Hydrochloride 

324380 (Adriamycin; 14-Hydroxydaunomycin, HCl) 

An anti-tumor antibiotic and a highly effective myotoxin that inhibits 

topoisomerase II (IC 50 = 00 nM). 


A potent antioxidant with anti-mutagenic and anti-carcinogenic properties. 

Inhibits DNA topoisomerases I and II (IC 50 = .8 mM and 2. mM, respectively). 

Acts as a potent inhibitor of PKA catalytic subunit (cAK) and PKC (IC 50 = 2 mM and 

8 mM respectively). 

Ellipticine 324688 (5,11-Dimethyl-6H-pyrido[4,3-b]carbazole) 

A topoisomerase II inhibitor. Acts as an intercalative alkaloid that stimulates 

topoisomerase II-mediated DNA breakage. 

Epirubicin 

Hydrochloride 

Etoposide 341205 (VP-16) 

324905 (4´-Epidoxorubicin, HCl) 

A stereoisomer of doxorubicin that exhibits reduced cardiotoxicity. Its antitumor 

actions are mediated by targeting topoisomerase II. 

A topoisomerase II inhibitor (IC 50 = 59.2 mM) that induces apoptosis in mouse 

thymocytes and in HL-60 human leukemia cells. 

Etoposide Phosphate 341206 A water-soluble derivative of the topoisomerase II inhibitor, etoposide 

(Cat. No. 34 205). 

Genistein 345834 (4´,5,7-Trihydroxyisoflavone) 

An inhibitor of protein tyrosine kinases (IC 50 = 2.6 mM for EGFR tyrosine kinase) 

that also inhibits topoisomerase II activity in vitro. 

Merbarone 445800 [NSC-336628; 5-(N-Phenylcarboxamido)-2-thiobarbituric Acid] 

An anticancer drug that inhibits the catalytic activity of DNA topoisomerase II 

(topo II) without damaging DNA or stabilizing DNA-topo II cleavable complexes 

(IC 50 = 20 mM for purified mammalian topoisomerase II versus IC 50 ~200 mM for 

topoisomerase I). 

Suramin, Sodium Salt 574625 A competitive inhibitor of reverse transcriptase that also blocks the activity of 

topoisomerase I and II. 

Topotecan, 

Hydrochloride 

614800 {9-[(Dimethylamino)methyl]-10-hydroxy-(20S)-camptothecin, HCl} 

A water-soluble, semi-synthetic derivative of camptothecin (Cat. No. 208925). 

A potent DNA topoisomerase I inhibitor. Has been shown to exhibit antitumor 

activity against several forms of cancer. 

0 mg $ 49 

500 mg $57 

0 mg $64 

5 mg $ 

25 mg $4 

5 mg $67 

20 mg 

50 mg 

$73 

$ 46 

25 mg $77 

50 mg 

200 mg 

$34 

$ 

mg $ 69 


Phone 800 628 8470 


83


Did you know Calbiochem carries a wide range of 

convenient ready-to-use Insolution Inhibitors? 

Ready-to-use, InSolution Protein Kinase Inhibitors 

Name Cat. No. Comments Size Price 

InSolution AMPK Inhibitor, Compound C 7 26 Supplied as a 0 mM ( mg/250 ml) solution of AMPK Inhibitor, Compound C 

(Cat. No. 7 260) in DMSO. Purity: ≥95% by HPLC. M.W. 399.5 

InSolution Casein Kinase I Inhibitor, D4476 2 8705 Supplied as a 0 mM ( mg/25 ml) solution of Casein Kinase I Inhibitor, D4476 

(Cat. No. 2 8696) in DMSO. Purity: ≥95% by HPLC. M.W. 398.4 

InSolution Casein Kinase II Inhibitor, DMAT 2 8706 Supplied as a 0 mM (5 mg/ .05 ml) solution of Casein Kinase II Inhibitor, DMAT 

(Cat. No. 2 8699), in DMSO. Purity: ≥95% by HPLC. M.W. 476.8 

InSolution GSK-3b Inhibitor VIII 36 557 Supplied as a 25 mM (5 mg/649 ml) solution of GSK-3b Inhibitor VIII (Cat. No. 

36 549) in DMSO. Purity: ≥95% by HPLC. M.W. 308.3 

InSolution JAK Inhibitor I 420097 Supplied as a 0 mM (500 mg/ 62 ml) solution of JAK Inhibitor I (Cat. No. 420099) 

in DMSO. Purity: ≥98% by HPLC. M.W. 309.3 

InSolution p38 MAP Kinase Inhibitor III 506 48 Supplied as a 0 mM ( mg/247 ml) solution of p38 MAP Kinase Inhibitor III 

(Cat. No. 506 2 ) in DMSO. Purity: ≥98% by HPLC. M.W. 404.5 

InSolution PD 58780 5 3036 Supplied as a 0 mM (500 mg/ 5 ml) solution of PD 58780 (Cat. No. 5 3035) in 

DMSO. Purity: ≥95% by HPLC. M.W. 330.2 

InSolution Rapamycin 5532 Supplied as a 5 mM (500 mg/ 09 ml) solution of Rapamycin (Cat. No. 5532 0) in 

DMSO. Purity: ≥98% by TLC. M.W.9 4.2 

InSolution Rho Kinase Inhibitor 555552 Supplied as a 0 mM (500 mg/ 28 ml) solution of Rho Kinase Inhibitor 

(Cat. No. 555550) in H 2 O. Purity: ≥95% by HPLC. M.W. 392.3 

InSolution VEGF Receptor 2 Kinase Inhibitor III 676498 Supplied as a 0 mM (500 mg/2 0 ml) solution of VEGF Receptor 2 Kinase 

Inhibitor III (Cat. No. 676487) in DMSO. Purity: ≥95% by HPLC. M.W. 238.3 

More online... www.calbiochem.com/insolution 

mg $72 

mg $ 2 

5 mg $90 

5 mg $84 

500 mg $83 

mg $ 2 

500 mg $ 07 

500 mg $95 

500 mg $90 

500 mg $73 

84 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Lipid Signaling 

Acetyl-CoA Carboxylase (ACC) Inhibitors 

Cyclooxygenases (COX) are bifunctional hemoproteins 

that catalyze both the bisoxygenation of arachidonic 

acid to form PGG 2 and the peroxidative reduction of 

PGG 2 to form PGH 2 . Hence, COX has two different active 

sites. On one side, it has the cyclooxygenase active 

site, and on the opposite side is an entirely separate 

peroxidase site, which is required to activate the heme 

groups that participate in the cyclooxygenase reaction. 

The enzyme complex is a dimer of identical subunits, 

two cyclooxygenase active sites and two peroxidase 

active sites. COX-1 is a constitutive enzyme associated 

with the endoplasmic reticulum. It is responsible 

for maintaining normal physiologic function and is 

considered as a “housekeeping” enzyme. COX-2 is an 

inducible enzyme mainly associated with the nuclear 

envelope and is primarily associated with inflammation. 

Several cytokines and growth factors increase the 

expression of COX-2, mainly at inflammatory sites, 

producing prostaglandins, which mediate inflammation, 

pain, and fever. Increased expression of COX-2 has been 

associated with increased incidence 

of colon and breast cancers. 

Inflammatory 

Non-steroidal anti-inflammatory Signaling 

drugs (NSAIDs) exert antiinflammatory 

and analgesic 

effects through the inhibition of 

prostaglandin synthesis by blocking 

COX activity. Traditional NSAIDs 

inhibit prostaglandin formation through 

the inhibition of both COX-1 and COX-2. 

Inhibition of COX-1 is not necessary for anti- 




CoEnzyme A, Trilithium Salt 234101 A reversible inhibitor of acetyl-CoA (IC 50 = 40 nM). 00 mg $ 27 

TOFA 613450 5-(Tetradecyloxy)-2-furoic acid 

A cell-permeable furoic acid compound that acts as a potent, reversible, and 

competitive inhibitor of acetyl-CoA carboxylase (ACC), a key enzyme involved 

in the fatty acid biosynthesis. Inhibits cellular fatty acid synthesis in a dosedependent 

manner (IC 50 = 4 mM in human breast cancer cell line MCF7). TOFAinduced 

reduction in malonyl-CoA is reported to offset the effect of C75 

(Cat. No. 34 325) on food intake in fasted mice and on apoptosis in tumor cells. 

Cyclooxygenase (COX) Inhibitors 

inflammatory and analgesic effects but is thought to 

account for much of the toxicity of traditional NSAIDs. 

Based on structural differences in the active sites 

of these two isozymes, several new drugs have been 

developed that specifically inhibit only COX-2 activity. 

COX-2 selective inhibitors have the potential to provide 

the traditional benefits of NSAID with significantly 

reduced incidence of endoscopic ulcers. The selective 

COX-2 inhibitors have great clinical significance because 

they can allow the preservation of COX-1 activity, which 

is essential in maintaining prostaglandins that are 

important for normal platelet function and protection 

of the gastrointestinal mucosa, and still inhibit COX-2 

to reduce inflammation and other pathologic processes. 

Due to the consideration of “inflammation as a 

factor” there has been an upsurge of interest in COX-2 

inhibitors as possible candidates for the treatment of 

Alzheimer's disease. NSAIDs are believed to inhibit 

human Ab aggregation in vitro and reverse the b-sheet 

conformation of preformed (continued…) 

PLA2 

Activation 

COX 

COX 

PGG 2 

Arachidonic 

Acid 

Prostaglandins 

Thromboxane 

Inflammation 

Pain 

Fever 

Hypertension 

5 mg $2 0 

Platelet 

Aggregation 


Phone 800 628 8470 


85


Cyclooxygenase (COX) Inhibitors, continued 

fibrils. Several epidemiological studies have indeed 

shown that groups of people taking NSAIDs, for 

unrelated conditions, such as rheumatoid arthritis, 

have a reduced incidence of Alzheimer's disease. More 

recently, coxibs, highly selective COX-2 inhibitors, have 

been linked to abnormalities in vascular function and 

regulation of hemostatis/thrombosis. This has rekindled 

interest in several other COX-2 inhibitors for pain 

management. 

Cyclooxygenase (COX) Inhibitors 

References: 

Fries, S., and Grosser, T., 2005. Hematology 445. 

Brune, K., and Hinz, B. 2004. Scand. J. Rheumatol. 33, . 

Johnson, A.J., et al. 200 . Adv. Enzyme Regul. 41, 22 . 

McGeer, P.L., and McGeer, E.G. 200 . Neurobiol. Aging 22, 799. 

Schnitzer, T.J. 200 . Am. J. Med. 110 (Suppl ), S46. 

Thomas, T., et al. 200 . NeuroReport 12, 3263. 

Weggen, S., et al. 200 . Nature 414, 2 2. 

Crofford, L.J., et al. 2000. Arthritis Rheum. 43, 4. 

Fournier, D.B., et al. 2000. J. Cell Biochem. 77, 97. 

Sugaya, K., et al. 2000. Jpn. J. Pharmacol. 82, 85. 


COX- Inhibitor, FR 22047 236005 {4,5-Bis(4-methoxyphenyl-2-[(1-methylpiperazin-4-yl)carbonyl]thiazole, 

Hydrochloride; 1-[(4,5-Bis(4-methoxyphenyl-2-thiazoyl)carbonyl]-4methylpiperazine, 

Hydrochloride; FR 122047} 

A potent, cell-permeable and selective inhibitor of COX- (IC 50 = 28 nM; human 

recombinant COX- ). Does not significantly inhibit COX-2 (IC 50 = 65 mM; human 

recombinant COX-2). 

COX-2 Inhibitor I 236011 {LM-1685; Methyl [5-methylsulfonyl-1-(4-chlorobenzyl)-1H-2indolyl]carboxylate} 

A potent and selective inhibitor of COX-2 (IC 50 = 650 nM from human 

monocytes). Displays only very weak activity against COX- from human 

platelets (IC 50 > 0 mM) and in whole blood (IC 50 > 00 mM). 

COX-2 Inhibitor II 236012 {4-[(5-Difluoromethyl-3-phenyl)-4-isoxazolyl]benzenesulfonamide; SC-791} 

A cell-permeable isoxazolyl-benzenesulfonamide compound that acts as a 

potent and highly selective inhibitor of COX-2 both in vitro (IC 50 = 4 nM for 

hCOX-2 vs. 4 mM for hCOX- ) and in vivo. 

Curcumin, Curcuma longa L. 239802 [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] 

Inhibitor of 5-LOX (IC 50 = 8 mM) and COX (IC 50 = 52 mM). Exhibits antitumor 

and anti-inflammatory properties. 

Diclofenac, 4'-Hydroxy- 287845 {2-[((2´,6´-Dichloro-4´-hydroxy)phenyl)amino]benzeneacetic Acid; 4´-OHD} 

A metabolite of Diclofenac (Cat. No. 287840). Formed through oxidation of 

diclofenac by cytochrome P450 2C9. Specifically blocks COX-2 activity (IC 50 = 

6.9 nM). 

Diclofenac Sodium 287840 {2-[(2,6-Dichlorophenyl)amino]benzeneacetic Acid, Na} 

A potent inhibitor of COX- (IC 50 = 76 nM) and COX-2 (IC 50 = 26 nM). Strongly 

inhibits insoluble transthyretin (TTR) amyloid fibril formation. 

DuP-697 317500 [5-Bromo-2-(4-fluorophenyl)-3-(4-(methylsulfonyl)phenyl)thiophene] 

A potent, irreversible, and time-dependent COX-2 inhibitor. Exhibits over 50-fold 

greater inhibitory potency against human and murine recombinant COX-2 (IC 50 = 

80 nM and 40 nM at 5 and 0 minutes, respectively) than COX- (IC 50 = 9 mM). 

Ebselen 324483 [2-Phenyl-1,2-benzisoselenazol-3(2H)-one; PZ51] 

A neuroprotective antioxidant that acts as a non-selective inhibitor of the 

cyclooxygenases. An excellent scavenger of peroxynitrite, and a glutathione 

peroxidase mimetic. 

ETYA 434741 (5,8,11,14-Eicosatetraynoic Acid) 

Inhibits COX (ID 50 = 8 mM), 5-LOX (ID 50 = 0 mM), 2-LOX 

(ID 50 = 300 nM), and 5-LOX (ID 50 = 200 nM) in whole cells. 

More online... www.calbiochem.com/inhibitors/cox 

Flurbiprofen 344079 {(±)-2-Fluoro-a-methyl[1,1´-biphenyl]-4-acetic Acid; U-27182} 

A non-steroidal anti-inflammatory agent that acts as a potent, but non-selective 

COX inhibitor (IC 50 = 5 nM for LPS-induced COX in human peripheral blood cells). 

Reduces Ab loads and Congo Red staining in APP+PS transgenic mice. 

5 mg $ 30 

5 mg $ 73 

5 mg $ 8 

00 mg $35 

00 mg $ 03 

g $28 

5 mg $ 69 

5 mg $64 

20 mg $203 

00 mg $38 

86 Orders Phone 800 854 34 7 


Fax 800 776 0999 






(±)-Ibuprofen 401003 {[(±)-2-(4-Isobutylphenyl)-propionic Acid} 

A competitive, and non-selective COX inhibitor (IC 50 = 4.8 mM for COX- and 

223 mM for COX-2). Decreases the total Ab secretion (Ab 40 and Ab 42 ) in human 

neuronal cells and offers neuroprotection against glutamate-, nitric oxide-, and 

superoxide-induced damage. 

Indomethacin 405268 [1-(p-Chlorobenzoyl)-2-methoxy-3-methyl-1H-indole-3-acetic Acid] 

A non-steroidal anti-inflammatory, anti-pyretic agent. Non-selective COX 

inhibitor (IC 50 = 740 nM for COX- and 970 nM for COX-2). Reported to reduce 

Ab 42 load independently of COX inhibition. 

Indomethacin Amide, 

N-Octyl- 

Indomethacin Ester, n- 

Heptyl- 

Indomethacin Ester, 4- 

Methoxyphenyl- 

405270 [1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-octylacetamide] 

An N-octylamide derivative of Indomethacin (Cat. No. 405268) that acts as a 

potent and selective COX-2 inhibitor (IC 50 = 40 nM) compared to COX- 

(IC 50 = 66 mM). 

405269 [1-(p-Chlorobenzoyl)-2-methoxy-3-methyl-1H-indole-3-acetic Acid, n-Heptyl Ester] 

A heptyl ester derivative of Indomethacin (Cat. No. 405268) that acts as a potent 

and selective COX-2 inhibitor (IC 50 = 40 nM) compared to COX- (IC 50 > 66 mM). 

405271 [1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic Acid, 4- 

Methoxyphenyl Ester] 

A 4-methoxyphenyl ester derivative of Indomethacin (Cat. No. 405268) that 

acts as a potent and selective COX-2 inhibitor (IC 50 = 40 nM) compared to COX- 

(IC 50 > 66 mM). 

Kaempferol 420345 (3,4´,5,7-Tetrahydroxyflavone) 

A phytoestrogen that offers protection against Ab 25–35 -induced cell death in 

neonatal cortical neurons. Blocks Ab-induced activation of caspase-2, -3, -8, 

and -9. Acts as an inhibitor of COX- (IC 50 = 80 mM) and COX-2 (IC 50 ~ 5 mM). 

Meloxicam 444800 [4-Hydroxy-2-methyl-N-(5-methyl-2-thiazoyl)-2H-1,2-benzothiazine-3carboxamide-1,1-dioxide] 

Preferentially inhibits COX-2 (IC 50 = 4.7 mM) relative to COX- (IC 50 = 36.6 mM). 

Niflumic Acid 481987 {2-[(3-Trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic Acid; UP-83} 

A selective inhibitor of COX-2 (K i = 20 nM for sheep placental COX-2). 

5-Nitro-2-(3-phenylpropylamino)benzoic 

Acid 

484100 (NPPB) 

A COX inhibitor (IC 50 = 8 µM) that also acts as a potent Cl – channel blocker 

(IC 50 = 00 nM - 00 mM), depending on channel subtype and assay method. 

NS-398 349254 [N-(2-Cyclohexyloxy-4-nitrophenyl)methanesulfonamide] 

Selective inhibitor of COX-2 (IC 50 = 3.8 mM for sheep placental COX-2). 

Reduces neuronal damage following a stroke. 

N Pterostilbene, Pterocarpus 

marsupium 

Radicicol, Diheterospora 

chlamydosporia 

523310 (trans-3,5-Dimethoxy-4´-hydroxystilbene) 

A cell-permeable methoxylated analog of Resveratrol (Cat. No. 554325) that 

inhibits COX- and COX-2 activities (IC = 9.8 mM and 83.9 mM, respectively). 

50 

553400 Inhibits the expression of COX-2 (IC = 27 nM) without affecting COX- 

50 

expression in LPS-stimulated macrophages. 

Resveratrol 554325 (trans-3,4´,5-Trihydroxystilbene) 

A phenolic product with antifungal, antitumor, and antioxidative properties. 

A specific inhibitor of COX- (ED = 5 mM). Also inhibits the hydroxyperoxidase 

50 

activity of COX- (ED = 3.7 mM). 

50 

SC-560 565610 [5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] 

A highly potent and selective inhibitor of COX- (IC = 9 nM). Inhibits COX-2 

50 

activity only at higher concentrations (IC = 6.3 mM). 

50 


A cytokine-suppressive anti-inflammatory drug that also acts as an inhibitor of 

both COX-2 and 5-LOX. An inhibitor of p38 MAP kinase activation. 

Sodium Salicylate 567630 (NaSal; Salicylic Acid, Na) 

A cell-permeable, non-steroidal anti-inflammatory agent that inhibits COX-2 

and inducible NOS (iNOS) transcription independently of NF-kB activation. 

g $43 

0 g $76 

5 mg $ 03 

5 mg $ 03 

5 mg $ 03 

25 mg $73 

00 mg $ 07 

g $39 

0 mg $62 

5 mg $ 3 

0 mg $ 47 

500 mg $75 

25 mg $4 

5 mg $ 04 

5 mg $ 23 

5 g $33 


Phone 800 628 8470 


87




Sulindac 574100 {Aflodac; (Z)-5-Fluoro-2-methyl-1-[p-(methylsulfinyl)benzylidene]indene-3-acetic 

Acid; MK-231} 

A prodrug that is metabolized to a pharmacologically-active sulfide derivative 

that potently inhibits COX-2 activity. Inhibits chemical carcinogenesis in rodent 

models and causes regression of adenomas by an apoptotic mechanism. 

g $46 

Sulindac Sulfide 574102 {(Z)-5-Fluoro-2-methyl-1-[p-(methylthio)benzylidene]indene-3-acetic Acid} 

A selective inhibitor of COX- (ID = 500 nM) versus COX-2 (ID = 4 mM). 

50 50 

Reduces Ab load independently of COX inhibition. 

42 

5 mg $67 

Sulindac Sulfone 574105 {Exisulind; FGN-1; (Z)-5-Fluoro-2-methyl-1[p-(methylsulfonyl)benzylidene]indene- 

3-acetic Acid} 

A sulfone metabolite of Sulindac (Cat. No. 574 00) that has anti-cancer 

properties but lacks COX inhibitory activity. Also inhibits cell growth and 

induces apoptosis. 

5 mg $67 

Cyclooxygenase Inhibitor Set 

Provided as a 4 vial set. Each set contains 00 mg of Meloxicam (Cat. No. 

444800), and 5 mg each of NS-398 (Cat. No. 349254), SC-560 (Cat. No. 

5656 0), and Sulindac Sulfide (Cat. No. 574 02). 

Cat. No. 239783 1 set $309 

Fatty Acid Amide Hydrolase Inhibitors 


0 mg $63 

FAAH Inhibitor I 341248 4-Benzyloxyphenyl-n-butylcarbamate, Fatty Acid Amide Hydrolase Inhibitor I, URB532 

A cell-permeable carbamate compound that acts as a potent, selective, and 

irreversible inhibitor of fatty acid amide hydrolase (FAAH; IC 50 = 396 nM in 

brain membranes). Shown to block anandamide (Cat. No. 72 00) breakdown in 

cultured rat cortical neurons (IC 50 = 2 4 nM) and inhibit brain FAAH activity 

(ID 50 = 0.6 mg/kg) and modulate anxiety in rats. 

FAAH Inhibitor II 341249 3′-Carbamoyl-biphenyl-3-yl-cyclohexylcarbamate; Cyclohexylcarbamic acid-3′carbamoyl-biphenyl-3-yl 

Ester; URB597 

A cell-permeable carbamate compound that acts as a potent, selective, and 

irreversible inhibitor of fatty acid amide hydrolase (FAAH; IC = 4.6 nM in brain 

50 

membranes). Shown to block anandamide (Cat. No. 72 00) breakdown in rat 

cortical neurons (IC = 500 pM) and modulate anxiety in rats (IC = 0. 5 mg/kg). 

50 50 

Fatty Acid Synthase Inhibitors 

5 mg $60 


Arachidonylserotonin 181350 AA-5-HT; N-Arachidonyl-5-hydroxytryptamine 

A novel synthetic arachidonic acid derivative that potently inhibits anandamide 

hydrolysis in both cell-free preparations and intact cells without affecting 

anandamide uptake. 

5 mg $74 

Cerulenin, Cephalosporium 219557 (2R, 3S)-2, 3-epoxy-4-oxo-7, 10-trans, trandocecadienamide 

5 mg $77 

caerulens 

A fungal toxin that binds to and irreversibly inhibits fatty acid synthase activity. 

Fatty Acid Synthase 

341325 C75; 3-Carboxy-4-octyl-2-methylenebutyrolactone; trans-4-Carboxy-5-octyl-3- 

mg $70 

Inhibitor, C75 

methylenebutyrolactone 

A cell-permeable a-methylene-g-butyrolactone compound that potently 

inhibits FAS (fatty acid synthase) activity and stimulates CPT- (carnitine 

palmitoyltransferase- ), two key enzymes involved in the fatty acid biosynthesis. 

Acts centrally (reduces NPY expression) and peripherally (activates CPT- and 

fatty acid oxidation activity) to cause reduced food intake and body weight in 

mice. Promotes cell cycle arrest in human cancer cells culminating in apoptosis. 

5 mg $244 

88 Orders Phone 800 854 34 7 


Fax 800 776 0999 


HMG-CoA (3-Hydroxy-3-Methylglutaryl Coenzyme A) 

Reductase Inhibitors 

HMG-CoA reductase catalyzes the 4-electron reduction 

of HMG-CoA to CoA and mevalonate, with oxidation of 

two molecules of NADPH. Regulation of the expression 

of hepatic HMG-CoA reductase is critical in maintaining 

normal cholesterol levels in serum and tissues. 

HMG-CoA reductase inhibitors (statins) are competitive 

inhibitors of this enzyme and have hypocholesterolemic 

properties. These inhibitors have close resemblance 

to HMG-CoA. During cholesterol biosynthesis they 

competitively inhibit the conversion of HMG-CoA to 

mevalonate, thereby reducing cholesterol biosynthesis 

in hepatic cells. This results in the enhanced synthesis of 

LDL-C receptors and increased uptake of LDL-C particles, 

which enhances cholesterol clearance from the plasma. 

Ultimately, LDL-C and total cholesterol concentrations 

are reduced. 

HMG-CoA (3-Hydroxy-3-Methylglutaryl Coenzyme A) Reductase Inhibitors 



HMG-CoA reductase inhibitors differ in their 

pharmacokinetic properties and drug interaction 

profiles. For example, Lovastatin and Simvastatin are 

extensively metabolized by CYP3A4, an isozyme of the 

P450 system, and thus have the potential to interact 

with other drugs competing for or inhibiting this 

isoform. Both Lovastatin and Simvastatin are prodrugs 

in the lactone form and must be converted to active 

metabolites by the liver. On the other hand, pravastatin 

is not extensively metabolized by the P450 system. It 

is administered in its active hydroxyl acid form and is 

more hydrophilic and less protein-bound. 


Cerulenin, 

Cephalosporium 

caerulens 

219557 An antifungal antibiotic that inhibits sterol and fatty acid biosynthesis. In fatty 

acid synthesis, reported to bind in equimolar ratio to b-keto-acyl-ACP synthase. 

In sterol synthesis, inhibits HMG-CoA synthetase activity. 

Fluvastatin, Sodium Salt 344095 {(±)-(3R´,5S´,6E)-7-[3-(4-Fluorophenyl)-1-isopropylindol-2-yl]-3,5-dihydroxy-6heptenoate, 

sodium} 

A synthetic HMG-CoA reductase inhibitor (IC 50 = 40– 00 nM for human liver 

microsomes) that acts as anti-hypercholesterolemic agent. 

Lovastatin 438185 (Mevinolin; MK-803) 

An anti-hypercholesterolemic agent that inhibits the activity of 3-hydroxy- 

3-methylglutaryl coenzyme A (HMG-CoA) reductase. 

Lovastatin, Sodium Salt 438186 Carboxylate form of Lovastatin (Cat. No. 438 85) that is active in whole cells and 

cell-free assays. 

Mevastatin 474700 (Compactin) 

An antibiotic that acts as a potent inhibitor of HMG-CoA reductase, thus 

suppressing Ras farnesylation. 

Mevastatin, Sodium Salt 474705 Carboxylate form of Mevastatin (Cat. No. 474700) that is active in whole cells 

and in cell-free assays. 

Pravastatin, Sodium Salt 524403 {(bR,dR,1S,2S,6S,8S,8aR)-1,2,6,7,8,8a-Hexahydro-b,d,6-trihydroxy-2methyl-8[(2S)-2-methyl-1-oxobutoxyl]-1-naphthaleneheptanoic 

Acid Na; 3b- 

Hydroxycompactin, Na} 

A water-soluble, competitive inhibitor of HMG-CoA reductase that potently 

blocks in vivo cholesterol synthesis (K i ~ nM). 

Simvastatin 567020 (MK-733) 

A lipophilic HMG-CoA reductase inhibitor that blocks Ras function through 

inhibition of farnesylation. 

Simvastatin, 

Sodium Salt 

More online... www.calbiochem.com/inhibitors/HMG 

567021 Carboxylate form of Simvastatin (Cat. No. 567020) that is active in whole cells 

and in cell-free preparations. 

5 mg $77 

25 mg $ 73 

25 mg $98 

5 mg $ 40 

50 mg $87 

5 mg $96 

25 mg $72 

50 mg $ 64 

5 mg $ 40 


Phone 800 628 8470 


89


Lipase Inhibitors 


N Lipase Inhibitor, THL 437701 Orlistat 

A cell-permeable, reactive b-lactone compound that acts as a selective, 

tight-binding irreversible inhibitor of gastric and pancreatic lipases with 

minimal activity against amylase, trypsin, chymotrypsin, and phospholipase A 2 . 

Covalently modifies a serine residue at the catalytic active site and partially 

N Monoacylglycerol Lipase 

Inhibitor, URB602 

inhibits the hydrolysis of triglycerides. Also potently inhibits the thioesterase 

app domain of fatty acid synthase (FAS; K ~ 00 nM) and induces apoptosis in 

i 

prostate carcinoma cells. 

475740 A cell-permeable compound that acts as a selective noncompetitive inhibitor of 

monoacylglycerol lipase (MGL; IC 50 = 28 mM for rat brain). Only minimally affects 

the activities of diacylglycerol lipase, FAAH and COX-2. 

Want to remove Lipids and Lipoproteins 

from your Plasma or Serum samples? 

PHM-L LIPOSORB Absorbent 

Designed to selectively remove lipoproteins from plasma or serum by 

batch procedure or column chromatography while antibody content and 

coagulation factors remain intact. Directly applicable with no further 

additions, affording improved serum or plasma stability. Has very low 

solubility in most solvents and has excellent chemical stability in acids 

and bases. PHM-L LIPOSORB Absorbent is resistant to enzymatic 

degradation and to activation of coagulation factors, is heat stable 

and can be sterilized by autoclaving ( 20˚C) without altering its binding 

capacity. Has high capacity with no volume limitation and is simple 

to use without expensive apparatus. Offers significant technical 

advantages over phenylagarose. One gram of absorbent is sufficient to 

remove lipids from 25 ml of serum or ascites. 

Cat. No. 524371 1 g 

10 g 

$45 

$285 

50 mg $93 

0 mg $98 

90 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Lipoxygenase (LOX) Inhibitors 

Lipoxygenases (LOX) belong to a heterogenous family 

of lipid-peroxidizing enzymes and are involved in 

the biosynthesis of mediators of inflammation. Based 

on their regiospecificity during interaction with 

substrates, LOX have been classified as 5-, 8-, 12-, and 

15-LOX. They insert oxygen at carbon 5, 8, 12 or 15 

of arachidonic acid, forming 5S-, 8S-, 12S-, or 15Shydroperoxyeicosatetraenoic 

acid (5-, 8-, 12-, or 15- 

HPETE). HPETEs can be further reduced by glutathione 

peroxidase to the hydroxy forms (5-, 8-, 12-, 15-HETE), 

respectively. 5-LOX is a dioxygenase that catalyzes the 

incorporation of molecular oxygen into arachidonic acid 

(oxygenase activity), producing HPETE and then forms 

the unstable epoxide LTA4 (LTA4 synthase activity). 

This is followed by the insertion of molecular oxygen 

at position C5, converting LTA4 to either 5(S)-hydroxy- 

6-trans-8, 11,14-cis-eicosatetranoic acid (5-HETE) or 

leukotrienes. Hydrolytic attack of LTA4 by leukotriene 

A4 hydrolase yields LTB4, a potent neutrophil 

chemoattractant and stimulator of leukocyte adhesion 

to endothelial cells. LTA4 can be conjugated with 

glutathione to form LTC4 by the action of LTC4 synthase. 

5-LOX pathway has been implicated in the development 

and progression of human cancers. Hence, 5-LOX 

inhibitors have been sought for their chemopreventive 

effects. Inhibition of 5-LOX activity is shown to block 

prostate cancer cell proliferation. 

12-LOX exists in three distinct forms: the leukocytetype, 

the platelet-type, and the epidermal form. The 

Lipoxygenase (LOX) Inhibitors 



platelet-type 12-LOX converts arachidonic acid to 

12-(S)-HETE. The leukocyte-type 12-LOX metabolizes 

arachidonic acid or linoleic acid to either 12(S)- 

HETE or 15(S)-HETE. The epidermal form of 12-LOX 

converts arachidonic acid to 12-HETE and 15-HETE. 

12-LOX has been shown to be involved in both cancer 

cell proliferation and survival. Inhibition of 12-LOX 

blocks cell proliferation and induces apoptosis in 

carcinosarcoma cells. 8-LOX is expressed in the skin 

after irritation or treatment with tumor promoters. 

Compared with other LOX enzymes, 8-LOX has received 

little attention for its role in carcinogenesis and cancer 

growth. 15-LOX exists as two isozymes, 15-LOX-1 and 

15-LOX-2. It converts arachidonic acid to 15-HPETE 

which is then reduced by glutathione peroxidase to 15- 

HETE. The preferred substrate for 15-LOX-1 and 15-LOX- 

2 are linoleic acid and arachidonic acid, respectively. The 

15- LOX-1 product, 13-S-HODE, is reported to enhance 

cell proliferation and potentiate the mitogenic response 

to EGF in different cell types. 15-LOX has also been 

implicated in the pathogenesis of altherosclerosis. 

References: 

Kuhn, H. 2005. Expert Rev. Cardiovas. Ther. 3, 099. 

Zhao, L., and Funk, C. D. 2004. Trends Cardiovasc. Med. 14, 9 . 

Funk, C.D. 200 . Science 294, 87 . 

Shureiqi, I., and Lippman, S.M. 200 . Cancer Res. 61, 6307. 

Kuhn, H., et al. 999. Adv. Exp. Med. Biol. 447, 5. 

Yamamoto, S., et al. 999. Adv. Exp. Med. Biol. 447, 37. 

Anderson, K.M., et al. 996. Anticancer Res. 16, 2589. 

Funk. C.D., et al. 996. J. Biol. Chem. 271, 23338. 


N Acetyl- -keto-b- 

Boswellic Acid, 

Boswellia serrata 

110123 (3-O-Acetyl-11-keto-b-Boswellic Acid; AKBA; AKbBA) 

A cell-permeable, nonredox, noncompetitive inhibitor of 5-lipoxygenase 

(IC 50 = .5 mM in rat PMNLs), and calf thymus topoisomerase I ( ≥ 0 mM). 

Arachidonylserotonin 181350 AA-5-HT, N-Arachidonyl-5-hydroxytryptamine 

Irreversibly inactivates soybean 5-lipoxygenase (K i ~20 mM). 

More online... www.calbiochem.com/inhibitors/LOX 

Baicalein 196322 (5,6,7-Trihydroxyflavone) 

Flavone that inhibits the activity of 2-LOX (IC 50 = 20 nM) and reverse 

transcriptase. Reduces leukotriene biosynthesis and the release of lysosomal 

enzymes. 

Caffeic Acid 205546 (3,4-Dihydroxycinnamic Acid) 

An inhibitor of neutrophil elastase (IC 50 = 93 mM). Also acts as a selective, 

non-competitive inhibitor of 5-lipoxygenase (ID 50 = 3.7 mM), glutathione 

S-transferases, and xanthine oxidase. 

Curcumin, Curcuma longa L. 239802 [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] 

Inhibitor of 5-LOX (IC 50 = 8 mM) and COX (IC 50 = 52 mM). Exhibits antitumor 

and anti-inflammatory properties. 

5 mg $ 68 

5 mg $74 

0 mg $77 

500 mg $48 

00 mg $35 


Phone 800 628 8470 


9


Lipoxygenase (LOX) Inhibitors, continued 


Eicosapentaenoic Acid 324875 (C20:5 w-3; 5,8,11,14,17-Eicosapentaenoic Acid; EPA) 

A fatty acid isolated from microscopic algae that acts as an antihyperlipoproteinenic 

agent. Inhibits 5-LOX and reduces thromboxane A2 

production. 

ETYA 434741 (5,8,11,14-Eicosatetraynoic Acid) 

A cell-permeable inhibitor of COX (ID 50 = 8 mM), 5-LOX (ID 50 = 0 mM), 2-LOX 

(ID 50 = 300 nM), and 5-LOX (ID 50 = 200 nM) in whole cells. Also acts as a 

modulator of Ca 2+ entry into cells. 

Hinokitiol 377230 (4-Isopropyltropolone; b-Thujaplicin) 

A cell-permeable metal ion chelator that also acts as a reversible inhibitor of 

2-LOX in platelets (IC 50 = 00 nM). 

Ketoconazole 420600 {cis-1-Acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3dioxolan-4-yl]methoxy]phenyl]piperazine; 

R-41400} 

An antifungal agent that acts as an inhibitor of 5-LOX (IC = 26 mM) and 

50 

thromboxane synthase. 

MK-886 475889 {3-[1-(p-Chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2,2dimethylpropanoic 

Acid, Na} 

A cell-permeable, potent and specific inhibitor of leukotriene biosynthesis 

(IC = 02 nM). Prevents the activation of 5-LOX by binding to 5-LOX-activating 

50 

protein (FLAP); however, it does not affect 5-LOX activity in cell-free systems. 

NDGA, Larrea divaricata 479975 (Nordihydroguaiaretic Acid) 

An antioxidant and a selective LOX inhibitor (IC = 200 nM, 30 mM, and 30 mM 

50 

for 5-LOX, 2-LOX, and 5-LOX, respectively) over COX (IC = 00 mM). 

50 

Ro 06-9920 557550 A cell-permeable, irreversible inhibitor of IkBaee ubiquitination (IC = 2.3 mM) 

50 

that also inhibits the activity of 5-lipoxygenase (89% at 0 mM). 


A cytokine-suppressive anti-inflammatory drug that also acts as an inhibitor of 

both COX and 5-LOX. 

25 mg $83 

20 mg $203 

50 mg $43 

50 mg $75 

5 mg $90 

250 mg $46 

92 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

$72 

$25 

5 mg $ 23

Phospholipase Inhibitors 

Several signal transduction processes in cells utilize 

lipid-derived second messengers. These molecules are 

generated by the action of phospholipases on cellular 

lipids. Phospholipase A 2 (PLA 2 ) hydrolyzes the acyl 

group from the sn-2 position of glycerophospholipids. 

Two major types of PLA 2 are found in cells: the cytosolic 

form (cPLA 2 ) and the secretory form (sPLA 2 ). cPLA 2 , an 

85 kDa enzyme, preferentially hydrolyzes phospholipids 

containing arachidonate at the sn-2 position and 

provides free arachidonic acid for the synthesis of 

eicosanoids. cPLA 2 is found in a variety of cells where 

it acts as a receptor-regulated enzyme that can mediate 

agonist-induced arachidonic acid release. It is activated 

by low levels of Ca 2+ . sPLA 2 , following its release from 

cells, plays an important role in inflammation and in 

antimicrobial defense. However, excessive activity of 

sPLA 2 has been shown to result in tissue damage and is 

linked to organ failure associated with critical illness. 

Phospholipase Inhibitors 



PLA 2 inhibitors are considered as desirable candidates 

for control and management of diseases related to 

eicosanoid production, such as allergy, inflammation, 

thrombosis, airway secretion, and cell proliferation. 

Phospholipase C (PLC) is another important member 

of the family that controls the production of inositol- 

1,4,5- trisphosphate (IP 3 ). IP 3 is involved in cytosolic 

Ca 2+ release and diacylglycerol (DAG) production, both of 

which activate protein kinase C. Phospholipase D (PLD) 

catalyzes the hydrolysis of phosphatidylcholine to form 

phosphatidic acid (PA) and released choline headgroup. 

The PA can itself act as a signal molecule by activating a 

PA-activated kinase, or can be hydrolyzed to form DAG 

by the action of PA phosphohydrolase. 


AACOCF 3 100109 (Arachidonyltrifluoromethyl Ketone) 

A cell-permeable trifluoromethyl ketone analog of arachidonic acid. Potent 

and selective slow-binding inhibitor of human cytosolic (85 kDa) PLA 2 . Causes 

a significant reduction in thromboxane B 2 production in thrombin-stimulated 

platelets. 

ACA 104550 [N-(p-Amylcinnamoyl)anthranilic Acid] 

Inhibits epinephrine-stimulated thromboxane production (86% at 3.5 mM) via 

inhibition of PLA 2 in human platelets. Possesses moderate leukotriene antagonist 

activity. 

Aristolochic Acid 182300 A : mixture of aristolochic acids I and II. Inhibits PLA 2 from various snake 

venoms as well as human platelet and synovial fluid PLA 2 . Also inhibits 

ionophore-stimulated PLA 2 activity (IC 50 = 40 mM) and Ca 2+ -dependent 

arachidonic acid released in human neutrophils. Exhibits greater inhibitory 

activity towards group II PLA 2 versus group I PLA 2 . 

D609, Potassium Salt 251400 (Tricyclodecan-9-yl-xanthogenate, K) 

Selective inhibitor of phosphatidylcholine-specific phospholipase C (Bacillus 

cereus, K i = 5– 0 mM). Does not inhibit (up to 50 mM) phosphatidylinositolspecific 

phospholipase C, PLA 2 , and PLD. Also inhibits the activity of 

sphingomyelinase. 

D609 Prodrug 251401 (S-Methyleneoxybutyryl D609) 

A cell-permeable prodrug form of D609 (Cat. No. 25 400) that displays reduced 

cytotoxicity towards normal cells, but enhanced potency in inducing apoptosis in 

tumor cells (LD 50 = 56.6 mM for U937 cells). 

ET- 8-OCH 3 341207 (Edelfosine; 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphorylcholine) 

A selective inhibitor of phosphatidylinositol-specific PLC (IC 50 = 5 mM) but has 

no significant effect on phosphatidylcholine-specific PLC or PLD. 

Isotetrandrine 419650 A biscoclaurine alkaloid that inhibits G-protein activation of phospholipase A 2 

but not phospholipase C or phospholipase D. 

Methyl Arachidonyl 

Fluorophosphonate 

More online... www.calbiochem.com/inhibitors/plipase 

454565 (MAFP) 

A selective, active site-directed, irreversible inhibitor of both calcium-dependent 

and calcium-independent cytosolic (85 kDa) PLA 2 , but not secretory PLA 2 . 

0 mg $87 

25 mg $84 

50 mg $50 

5 mg $ 07 

5 mg $ 63 

5 mg $80 

mg $77 

mg $77 


Phone 800 628 8470 


93


Phospholipase Inhibitors, continued 


MJ33 475865 [1-Hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol, Li] 

A novel, active-site directed, specific, competitive, and reversible inhibitor 

of PLA 2 . Shows high specificity for type I (pancreatic) and bee venom PLA 2 , 

but has relatively poor affinity for the type II human synovial PLA 2 . MJ33 has 

shown inhibitory activity against a low pH calcium-independent enzyme, as 

well as against the PLA 2 activity, which is responsible for permeability barrier 

homeostasis or esophagitis. 

Neomycin Sulfate 4801 An inhibitor of inositol phospholipid turnover. A non-specific PLC inhibitor. Also 

inhibits phophatidylcholine-PLD activity (IC 50 = 65 mM). 

Neomycin Sulfate, 

g-Irradiated, Tissue Culture 

Grade 

480100 An inhibitor of inositol phospholipid turnover. A non-specific PLC inhibitor. 

Also inhibits phophatidylcholine-PLD activity (IC 50 = 65 mM). 

PACOCF 3 506274 (Palmitoyl Trifluoromethyl Ketone) 

A novel Ca 2+ -independent PLA 2 inhibitor (IC 50 = 3.8 mM). May also inhibit 

Ca 2+ -dependent PLA 2 at higher concentrations (IC 50 = 45 mM). 

cPLA2a Inhibitor 525143 {N-{(2S,4R)-4-(Biphenyl-2-ylmethyl-isobutyl-amino)-1-[2-(2,4-difluorobenzoyl)benzoyl]-pyrrolidin-2-ylmethyl}-3-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)phenyl]acrylamide, 

HCl} 

A cell-permeable, highly specific, potent inhibitor of cytosolic PLA2a 

(IC 50 = .8 nM). Exhibits ~230-fold greater potency in enzyme assays and 

~3900-fold greater potency in cellular assays compared to AACOCF 3 

(Cat. No. 00 09). 

sPLA 2 -IIA Inhibitor I 525145 [c(2NapA)LS(2NapA)R, TFA] 

A highly hydrophobic cyclic pentapeptide that selectively binds and acts as a 

potent inhibitor of human type IIA secreted PLA 2 (IC 50 = 2.8 mM). Reported 

to effectively block sPLA 2 -IIA-induced PGE 2 production at 00 nM in human 

rheumatoid synoviocytes and is non-toxic at doses up to 0 mM. Does not affect 

the activities of porcine sPLA 2 -IB, Naja naja sPLA 2 -IB, or Crotalus durissus 

sPLA 2 -IIA even at 0 mM. 

Quercetin, Dihydrate 551600 (3,3´,4´,5,7-Pentahydroxyflavone) 

An inhibitor of PI 3-kinase (IC 50 = 3.8 mM) and phospholipase A2 (IC 50 = 2 mM). 

Also inhibits mitochondrial ATPase, phosphodiesterases, and PKC. 

Quinacrine, Dihydrochloride 551850 (Mepacrine) 

A phospholipase A 2 inhibitor that also inhibits the activity of monoamine 

oxidase. 

Spermine, 

Tetrahydrochloride 


Dihydro- 

5677 Polyamine that plays an important role in the regulation of cellular proliferation 

and differentiation. Acts as an inhibitor of PLC-a and an activator of PLC-d. 

300230 (Sphinganine) 

Biosynthetic precursor of sphingosine. Inhibits PKC in Chinese hamster ovary 

cells (IC 50 = 2.9 mM). 

ST638 567790 [a-Cyano-(3-ethoxy-4-hydroxy-5-phenylthiomethyl)cinnamide] 

A protein tyrosine kinase inhibitor (IC 50 = 370 nM) that also inhibits PLD activity 

in human neutrophils. 

U-73 22 662035 {1-[6-((17b-3-Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione} 

Inhibits agonist-induced PLC activation (IC 50 = .0–2. mM) in human platelets 

and neutrophils. 

U-73343 662041 {1-[6-((17b-3-Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione} 

Analog of U-73 22 (Cat. No. 662035) that acts as a very weak inhibitor of PLC. 

Suitable as a negative control. 

5 mg $89 

25 g $32 

20 ml $55 

5 mg $43 

500 mg $ 73 

mg $ 03 

00 mg $33 

00 mg $34 

5 g $ 45 

0 mg $79 

5 mg $ 28 

5 mg $95 

5 mg $95 

94 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Sphingomyelinase Inhibitors 

Ceramide, a sphingosine-based lipid-signaling molecule, 

has gained serious attention as an important signaling 

molecule in cell cycle, cell differentiation, apoptosis, and 

immune response. Ceramide is generated either through 

de novo synthesis mediated by ceramide synthase or 

through hydrolysis of membrane sphingomyelin by 

an acid or neutral sphingomyelinase. Acid and neutral 

sphingomelinases differ in their ion dependence, pH 

optima, and cellular localization. Recent evidence 

suggests that the activation of a non-specific lipid 

scramblase during apoptosis induces the flipping of 

sphingomyelin from the cell surface to the cytoplasm 

side of the plasma membrane where it is cleaved by 

neutral sphingomyelinase to generate ceramide. The 

production of ceramide induces blebbing of the plasma 

membrane and aids in rapid engulfment by phagocytes. 

Neutral sphingomyelinase-released ceramide has also 

been shown to be essential for capping of L-selectin in 

lymphocytes. 

Sphingomyelinase Inhibitors 



Some evidence exists indicating that acid 

sphingomyelinase deficient cells have defects in 

apoptotic signaling pathways. Sphingomyelin is 

usually rapidly broken down in the late endosomes and 

lysosomes. Hence, in acid sphingomyelinase deficiency, 

sphingomyelin may be kinetically trapped in lysosomes 

and disrupt endocytic trafficking of raft-associated 

cell surface signaling molecules. Defects in acid 

sphingomyelinase have also been linked to lysosomal 

storage disease known as Niemann-Pick disease, which 

results in progressive enlargement of liver and spleen. 

References: 

Cremesti, A.E., et al. 2002. FEBS Lett. 531, 47. 

Sillence, D.J. 200 . BMC Cell Biology 2, 24. 

Zhang, Y., et al. 200 . J. Biol. Chem. 276, 775. 

Tomiuk, S., et al. 998. Proc. Natl. Acad. Sci. USA 95, 3638. 


Chlorpromazine, 

Hydrochloride 

215921 {2-Chloro-10-[3´-(dimethylamino)propyl]phenothiazine, HCl} 

An inhibitor of calmodulin-dependent phosphodiesterase I (IC 50 = 7 mM) that 

acts as an inhibitor of lysosomal sphingomyelinase. 

3,4-Dichloroisocoumarin 287815 A serine protease inhibitor that blocks daunorubicin-induced neutral 

sphingomyelinase activation. 

Fumonisin B , Fusarium 

moniliforme 

344850 (FB 1 ) 

A cell-permeable mycotoxin that inhibits sphingolipid biosynthesis in rat kidney 

and in liver microsomes by inhibition of sphingosine N-acyltransferase (ceramide 

synthase; IC 50 = 00 nM). Preferentially inhibits sphingomyelin biosynthesis in 

neuronal cells. Exhibits carcinogenic properties. 

Gentamycin Sulfate 345814 A broad-spectrum antibiotic that reduces sphingomyelinase activity in 

fibroblasts. 

Manumycin A, Streptomyces 

parvulus 

444170 A potent and selective inhibitor of farnesyl transferase (IC 50 = 5 mM) that acts as 

an irreversible inhibitor of neutral sphingomyelinase. 

N-SMase Inhibitor, GW4869 567715 (GW554869A; GW69A; Sphingomyelinase, Neutral, Inhibitor GW4869) 

A cell-permeable, symmetrical dihydroimidazolo-amide that acts as a potent, 

specific, and non-competitive inhibitor of neutral sphingomyelinase (N-SMase) 

(IC 50 = mM, rat brain N-SMase). 

N a -Tosyl-Phe Chloromethyl 

Ketone 

Squalene-2,3-oxide Cyclase Inhibitor 

616387 (TPCK) 

A serine protease inhibitor that blocks daunorubicin-induced neutral 

sphingomyelinase activator and sphingomyelin hydrolysis. 

More online... www.calbiochem.com/inhibitors/sphingomyelinase 

500 mg $57 

0 mg $ 30 

250 mg 

g 

mg $69 

g $58 

mg $77 

mg $ 46 


AMO 6 8 1712 Anticholesterolemic agent that can be used as an inhibitor of squalene-2,3-oxide 

cyclase to study the action of squalene epoxidase in the microsomal cholesterol 

biosynthetic pathway. 

$39 

$ 0 

250 g $ 29 


Phone 800 628 8470 


95

Neurobiology/Neurodegeneration 


Amyloidogenesis Inhibitors 

Ab (b-amyloid) peptide is a major component of neuritic 

plaques and cerebrovascular amyloid deposits in the 

brains of patients with Alzheimer's disease (AD). The 

cellular origin of amyloid precursor protein (APP) that 

gives rise to Ab is now well understood. Morphological 

evidence suggests that APP-immunoreactive neurites, 

often capped by Ab deposits, are one of the major sources 

of parenchymal amyloid. However, other cells, including 


astroglia, microglia, and vascular cells, may contribute 

to the formation of Ab. A long-standing hypothesis has 

been that Ab deposits are neurotoxic and are causative 

factors in the development and progression of AD. Hence, 

the development of inhibitors of Ab fibrillogenesis has 

become an important area of research. 

More online... www.calbiochem.com/inhibitors/amyloidogenesis 


Ab 40 Fibrillogenesis Inhibitor 171581 [Ab16-20m; Ac-K(Me)LV(Me)FF-NH 2 ; Amyloid b 40 Fibrillogenesis Inhibitor] 

Cell-permeable pentapeptide based on the core domain of Ab, which 

contains N-methyl amino acids in alternate positions. Displays stability 

towards denaturation and is resistant to chymotrypsin. 

Ab 42 Fibrillogenesis Inhibitor I 171586 (Amyloid b 42 Fibrillogenesis Inhibitor I; iAb5; LPFFD) 

Design is based on the central hydrophobic region in the N-terminal 

domain of Ab. Binds to the monomeric/dimeric Ab peptides with high 

affinity (K d ~70 nM). 

Ab 42 Fibrillogenesis Inhibitor II 171587 (Amyloid b 42 Fibrillogenesis Inhibitor II; RVVIA-NH 2 ) 

Contains the C-terminal sequence of Ab 42 with Gly 38 to Arg substitution, 

which results in improved solubility and potency. 

Ab 42 Fibrillogenesis Inhibitor III 171588 (Amyloid b 42 Fibrillogenesis Inhibitor III; Ac-LPFFD-NH 2 ; iAb5p) 

A modified analog of Ab 42 Fibrillogenesis Inhibitor I (Cat. No. 7 586). 

Can cross the blood brain barrier. Exhibits greater stability against 

proteolytic degradation. 

Ab 42 Fibrillogenesis Inhibitor IV 171589 [Ac-LP-(NMe)-FFD-NH 2 ; Amyloid b 42 Fibrillogenesis Inhibitor IV; iAb5p-A1] 

A modified analog of the end protected Ab 42 Fibrillogenesis Inhibitor III 

(Cat. No. 7 588) that acts as a b-sheet breaker. Has increased 

in vivo metabolic stability (t ½ >24 hours in human plasma and in 

rat brain homogenate). 

Clioquinol 233165 (5-Chloro-7-iodo-8-hydroxyquinoline) 

A metal ion chelator that crosses the blood-brain barrier and acts as a 

neurotoxic antibiotic. Reported to dissolve senile plaques and reduce 

amyloid’s ability to clump together, apparently by trapping Cu 2+ and 

Zn 2+ that reduces the build-up of these deposits. 

Diclofenac Sodium 287840 A cell-permeable, non-selective cyclooxygenase inhibitor (IC 50 = 

60 nM and 200 nM for ovine COX- and COX-2 respectively) and potent 

non-steroidal anti-inflammatory drug with analgesic activity. Strongly 

inhibits insoluble transthyretin (TTR) amyloid fibril formation. Also 

inhibits liver phenol sulfotransferase activity (IC 50 = 9.5 mM). 

Flurbiprofen 344079 A non-steroidal anti-inflammatory agent that acts as a potent 

cyclooxygenase inhibitor (IC 50 = 5 nM for LPS-induced COX in human 

peripheral blood cells). Reduces Ab loads and Congo Red staining in 

APP+PS transgenic mice. 

Genistein 345834 An isoflavone that acts as a potent inhibitor of transthyretin (TTR) 

tetramer dissociation and amyloidogenesis. Binds to TTR with negative 

cooperativity (K d = 40 nM; K d2 = .4 mM). Prevents acid-mediated fibril 

aggregation. 

96 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

$77 

$289 

5 mg $ 35 

5 mg $ 35 

5 mg $ 35 

5 mg $20 

g $45 

g $28 

00 mg $38 

20 mg 

50 mg 

$73 

$ 46





Niflumic Acid 481987 A phenolic product with antifungal, antitumor, and antioxidative 

properties. A specific inhibitor of COX- (ED = 5 mM). Also inhibits 

50 

the hydroxyperoxidase activity of COX- (ED = 3.7 mM). Strongly 

50 

inhibits insoluble transthyretin (TTR) amyloid formation. 

g $39 

Resveratrol 554325 A phenolic product with antifungal, antitumor, and antioxidative 

properties. A specific inhibitor of COX- (ED = 5 mM). Also inhibits 

50 

the hydroxyperoxidase activity of COX- (ED = 3.7 mM). Promotes 

50 

intracellular degradation of Ab peptide via a proteasome-dependent 

process. 

25 mg $4 


Phone 800 628 8470 


97


Cholinesterase Inhibitors 

A large number of autonomic neurons are cholinergic in 

nature. Cholinergic terminals contain a large number of 

small acetylcholine (ACh)-containing, membrane-bound 

vesicles concentrated near the synaptic end. Following 

their release from the pre-synaptic end, ACh 

molecules activate cholinoreceptors 

on the post-synaptic membrane. 

Acetylcholinesterase 

(AChE) is a tetrameric 

protein that catalyzes 

the hydrolysis of 

acetylcholine. The 

active site of AChE 

includes a serine 

hydroxyl group 

that is rendered 

more nucleophilic 

through the 

proton-acceptor 

action of a nearby 

histidine residue. The 

serine residue exerts 

a nucleophilic attack 

on the carbonyl carbon 

Cholinesterase Inhibitors 

Cardiovascular 

Vasodilation 

Reduced Cardiac Rate 

Reduced Force of Contraction 

Gastro-Intestinal 

Increased Peristalsis 

Enhanced Secretory Activity 

Sphincter Relaxation 

Glandular Secretions 

Increased Pancreatic Secretions 

Enhanced Salivary K + and Water Secretion 

Increased Adrenal Medullary Secretions 

Increased Lacrimal Secretions 

Urinary Bladder 

of acetylcholine. AChE inhibitors may act by either 

competitively blocking hydrolysis without reacting with 

the enzyme, or may acylate the serine hydroxyl group, 

forming a carbamyl ester, which is more stable than 

acetate and is less likely to abandon the 

active site of the enzyme. AChE 

inhibitors, which increase 

CHOLINE ESTERS 

MUSCARINIC 

EFFECTS 

Increased Uretural Peristalsis 

Reduced Bladder Capacity 

NICOTINIC 

EFFECTS 

CNS Effects 

Stimulation of CNS 

Excitation of Respiration 

Automomic Ganglia 

Excitation of Sympathetic 

and Parasympathetic Ganglia 

Muscle Contraction 

Neuromuscular 

the availability of 

acetylcholine in central 

synapses, as well as 

muscarinic agonists, 

have become the 

main approach 

to symptomatic 

treatment of patients 

with Alzheimer's 

disease (AD). These 

agents do not reverse the 

progression of the disease, 

but they do contribute to 

modest improvements in memory, 

thinking and reasoning skills in AD patients. 


Diisopropylfluorophosphate 30967 (DFP) 

98 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Junctions 

A potent irreversible inhibitor of serine proteases. Also irreversibly 

inactivates acetylcholinesterase. 

Galanthamine, Hydrobromide 345670 (Nivalin, HBr) 

A cholinesterase inhibitor and antimyasthenic agent that can partially 

reverse the effects of scopolamine-induced amnesia in rats. 

(±)-Huperzine A 385885 A synthetic, optically inactive, enantiomeric mixture that inhibits AChE 

activity and acts as a cholinomimetic. 

(–)-Huperzine A, Huperzia serrata 385886 Potently inhibits AChE (K i = 8 nM) in a mixed linear competitive manner. 

A more potent enantiomer with three-fold activity compared to the 

racemic mixture, (±)-Huperzine (Cat. No. 385885). 

Monoamine Oxidase Inhibitor 

More online... www.calbiochem.com/inhibitors/cholinesterase 

g $266 

20 mg $75 

mg $62 

250 mg $32 


Quinacrine, Dihydrochloride 551850 A non-specific phospholipase A 2 (PLA 2 ) inhibitor that inhibits 

monoamine oxidase activity. Also supresses glibenclamide-sensitve 

K + currents (IC 50 = 4.4 mM).. 

00 mg $34

Secretase Inhibitors 

Deposition of Ab is an early event in the pathogenesis of 

Alzheimer's disease (AD). The b-amyloid gene, located 

on chromosome 21, encodes a transmembrane amyloid 

precursor protein (APP), which gives rise to Ab. In 

normal healthy individuals, Ab peptides are present 

only in small quantities as soluble monomers that 

circulate in the cerebrospinal fluid and blood. However, 

in AD patients, the level of Ab peptides is significantly 

increased and they begin to accumulate as insoluble, 

fibrillar plaques. 

Processing of APP in vivo occurs by two major pathways. 

Cleavage of APP at the N-terminus of the Ab region 

by b-secretase and at the C-terminus by g-secretases 

represents the amyloidogenic pathway for processing of 

APP. b-secretase cleaves APP between residues Met 671 

and Asp 672 and yields Ab peptide plus the C99 fragment. 

Following b-secretase cleavage, a second cleavage occurs 

at the C-terminus of Ab peptide that releases Ab from C99. 

This cleavage occurs in the vicinity of residue 712 of the 

C-terminus. g-secretase can cleave the C-terminal region 

at either Val 711 or Ile 713 to produce a shorter Ab peptide 

(Ab 1-40 ) or the longer Ab peptide (Ab 1-42 ). The predominant 



form of Ab found in the cerebrospinal fluid is the shorter 

Ab 40 peptide. Despite its lower rate of synthesis, Ab 42 is the 

peptide that is initially deposited within the extracellular 

plaques of AD patients. In addition, Ab 42 is shown to 

aggregate at a much lower concentration than the Ab 40 

form. 

APP can also be processed by a-secretase (TACE), which 

cleaves within the Ab domain between Lys 687 and Leu 688 

and produces a large soluble a-APP domain and the Cterminal 

fragment containing P3 and C83. The latter can 

then be cleaved by g-secretase at residue 711 or 713 to 

release the P3 fragment. This pathway does not yield Ab 

peptide. Hence, shunting APP towards the a-secretase 

pathway may have a beneficial effect in lowering Ab 

peptide levels. 

The characterization of APP secretases during the past 

few years has provided significant advancement in 

therapeutic strategies that may lead to limiting the build 

up of Ab peptide in the brain and eliminate or delay 

the pathological effects of AD. Recent characterization 

of secretases has uncovered several common 

features, particularly their sensitivity to certain 

metalloproteinase inhibitors and up-regulation of their 

activity by phorbol esters. Presenilins and g-secretases 

are considered to be the best molecular targets for 

developing therapeutic agents that may minimize the 

debilitating effects of AD. Major targets in AD research 

are identifying the genetic and environmental factors 

responsible for b-amyloid build-up in nerve cells. 

References: 

Tomita, T. and Iwantsubo, T. 2006. Curr. Pharm. Res. 12, 66 . 

Steiner, H., et al. 2004. Curr. Alzheimer Res. 1, 75. 

Marlow, L., et al. 2003. J. Mol. Neurosci. 20, 233. 

Wilson, C.A., et al. 2003. J. Neurosci. Res. 74, 36 . 

Li, Y-M. 200 . Mol. Interv. 1, 98. 

Selkoe, D.J. 200 . Physiol. Rev. 81, 74 . 

Li, Y-M., et al. 2000. Nature 405, 689. 

Zhang, Z., et al. 2000. Nat. Cell Biol. 2, 463. 

Haass, C., and De Stooper, B. 999. Science 286, 9 6, 

Sinha, S., and Lieberburg, I. 999. Proc. Natl. Acad. Sci. USA 96, 049. 

Chen, M. 997. FEBS Lett. 417, 63. 

Selkoe, D. J. 997. Science 275, 630. 

Schweuner, D., et al. 996. Nat. Med. 8, 864. 

Citron, M., et al. 994. Proc. Natl. Acad. Sci. USA 91, 993. 

More online... www.calbiochem.com/inhibitors/secretase 


Phone 800 628 8470 


99


Secretase Inhibitors/Blockers of Ab Production 

Product Cat. No. Cell-permeable Reversible 

APP-b-Secretase Inhibitor 

[KTEEISEVN(Stat)VAEF] 

Calpain Inhibitor I 

(ALLN; Ac-LLNle-CHO) 

Calpain Inhibitor III 

(MDL 28 70; Z-VF-CHO) 

Calpeptin 

(Z-LNle-CHO) 

7 60 No Yes 

2087 9 Yes Yes 

208722 Yes Yes 

03-34-005 Yes Yes 

Indomethacin 405268 Yes No 

MG- 32 

(Z-LLL-CHO) 

InSolution OM99-2 

(EVNLYAAEF) 474790 Yes Yes 

496000 No Yes 

Pepstatin A Methyl Ester 5 6485 Yes Yes 

b-Secretase Inhibitor II 

(Z-VLL-CHO) 


b-Secretase Inhibitor III 

[EVN(Stat)VAEF-NH ] 2 

565780 No Yes 

b-Secretase Inhibitor IV 565788 Yes Yes 

N g-Secretase Inhibitor I 

(Z-LLNle-CHO) 


g-Secretase Inhibitor II 

[Boc-VI-NHCH(CH )-COCF CO-NHVI-OCH ; MW 67] 

3 2 3 


g-Secretase Inhibitor III 

(Z-LL-CHO) 


g-Secretase Inhibitor IV 

(2-Naphthoyl-VF-CHO) 

56576 Yes Yes 

g-Secretase Inhibitor V 

(Z-VF-CHO) 


g-Secretase Inhibitor VI 

{ -(S)-endo-N-( ,3,3)Trimethylbicyclo[2.2. ] 

hept-2yl)-4-fluorophenyl sulfonamide} 


g-Secretase Inhibitor VII 

(MOC-LL-CHO) 


g-Secretase Inhibitor IX (DAPT) 565770 Yes Yes 

N InSolution g-Secretase Inhibitor IX 565784 Yes Yes 

InSolution g-Secretase Inhibitor X 

(L-685,458) 

56577 Yes Yes 

g-Secretase Inhibitor XI 

(JLK6) 

565772 Yes No 

g-Secretase Inhibitor XII 

(Z-IL-CHO) 


g-Secretase Inhibitor XIII 

(Z-YIL-CHO) 


g-Secretase Inhibitor XIV 

[Z-C(t-Bu)-IL-CHO] 


g-Secretase Inhibitor XVI 

(DAPM) 


InSolution g-Secretase Inhibitor XVII 

(WPE-III-3 C) 


InSolution g-Secretase Inhibitor XIX 565787 Yes Yes 

N g-Secretase Inhibitor XX 565789 Yes Yes 

N g-Secretase Inhibitor XXI 565790 Yes Yes 

N g -Secretase Inhibitor I 

40 

(trans-3,5-DMC-IL-CHO) 


g -Secretase Inhibitor II 

40 

(Boc-GVV-CHO) 


00 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Secretase Inhibitors 




Bafilomycin A , Streptomyces 

griseus 

196000 A specific inhibitor of vacuolar-type H + -ATPase (V-type; K i = 500 pM) 

that selectively inhibits b-secretase activity. 

MG- 32 474790 (Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal; Z-LLL-CHO) 

A potent, reversible, and cell-permeable proteasome inhibitor 

(K i = 4 nM). Blocks the maturation of APP Swedish mutant (APPSw) 

preventing cleavage by b-secretase. Inhibits NF-kB activation 

(IC 50 = 3 mM). 

InSolution OM99-2 496000 (EVNLYAAEF) 

Supplied as a mM solution in 280 ml of DMSO. A peptidomimetic, 

highly potent, tight-binding transition-state analog inhibitor of 

b-secretase (K i = .6 nM, recombinant memapsin-2; K i = 9.58 nM, 

recombinant pro-memapsin 2). Designed from the template of the bsecretase 

site of Swedish b-amyloid precursor protein (APP) with Asp 

to Ala replacement. 

Pepstatin A Methyl Ester 516485 (Isovaleryl-V V-Sta-A-Sta-OCH ; PME) 

3 

A cell-permeable methyl ester derivative of Pepstatin A (Cat. No. 

5 648 ) that acts as a potent, non-competitive transition-state analog 

inhibitor of g-secretase (K = 50 nM, K = 320 nM for human g- 

is ii 

secretase at 20˚C; K is the inhibition constant for inhibitor binding to 

is 

the free enzyme and K is the inhibition constant for inhibitor binding to 

ii 

the Enzyme-Substrate complex). 

b-Secretase Inhibitor II 565749 (N-Benzyloxycarbonyl-Val-Leu-leucinal; Z-VLL-CHO) 

A potent, cell-permeable, and reversible inhibitor of b-secretase. 

Corresponds to the b-secretase cleavage site (VNL-DA) of the Swedish 

mutant Amyloid Precursor Protein (APP). Inhibits the formation of 

both Ab (IC = 700 nM) and Ab (IC = 2.5 mM in Chinese hamster 

total 50 -42 50 

ovary (CHO) cells transfected with wild-type APP75 ). 

b-Secretase Inhibitor III 565780 (H-EVNstatineVAEF-NH ; Inhibitor GL189) 

2 

A substrate analog inhibitor of b-secretase (BACE) that completely 

blocks the proteolytic activity (at 5 mM) in solubilized membrane 

fractions from BACE transfected MDCK cells. 

N b-Secretase Inhibitor IV 565788 Binds to BACE- active site and blocks its proteolytic activity 

(IC 50 = 5 nM for human BACE- ). 

g-Secretase Inhibitor I 565750 (Z-LLNle-CHO) 

A cell-permeable inhibitor of g-secretase activity. 

g-Secretase Inhibitor II 565755 (MW167) 

A cell-permeable, reversible, and selective peptidomimetic inhibitor of 

g-secretase (IC = 3 mM for total inhibition of Ab). Displays only weak 

50 

inhibitory activity against calpain II (IC = 00 mM in a purified enzyme 

50 

assay). 

g-Secretase Inhibitor III 565760 (N-Benzyloxycarbonyl-Leu-leucinal; Z-LL-CHO) 

A cell-permeable, specific, and reversible inhibitor of g-secretase 

that reduces the formation of both Ab (IC ~35 mM) and Ab in 

total 50 –42 

Chinese hamster ovary (CHO) cultures stably transfected with amyloid 

precursor protein-75 . Reported to be nontoxic in nature. 

g-Secretase Inhibitor IV 565761 [N-(2-Naphthoyl)-Val-phenylalaninal; 2-Naphthoyl-VF-CHO] 

A cell-permeable, reversible inhibitor of g-secretase. Inhibits the 

release of Ab (ED = 2.6 mM) and Ab (ED = 2.7 mM) in HEK293 

x-40 50 x-42 50 

cells stably transfected with the APP Swedish mutants. 

g-Secretase Inhibitor V 565762 (N-Benzyloxycarbonyl-Leu-phenylalaninal; Z-LF-CHO) 

A cell-permeable, reversible inhibitor of g-secretase. Reported to inhibit 

the release of Ab (ED = 5.0 mM) in HEK293 cells stably transfected 

x-40 50 

with the APP Swedish mutants. 

g-Secretase Inhibitor VI 565763 {1-(S)-endo-N-(1,3,3)-Trimethylbicyclo[2.2.1]hept-2-yl)-4-fluorophenyl 

Sulfonamide} 

A cell-permeable inhibitor of Ab production (IC = .8 mM). 

42 50 

Treatment of HEK293 cells with this inhibitor results in an increase in 

b-secretase-cleaved APP fragments and secreted APP a. s 

0 mg $ 7 

mg 

5 mg 

$34 

$98 

250 mg $329 

mg $67 

mg 

5 mg 

$52 

$ 97 

500 mg $93 

mg $ 49 

mg $ 04 

mg $ 74 

mg 

5 mg 

$52 

$203 

mg $99 

mg $99 

5 mg $ 50 


Phone 800 628 8470 


0


Secretase Inhibitors, continued 


g-Secretase Inhibitor VII 565768 [Compound A; MOC-LL-CHO (MOC = menthyloxycarbonyl)] 

A cell-permeable, reversible inhibitor of Ab and p3 secretion (Ab 40 

IC 50 = 2.3 mM; Ab 42 IC 50 = 3 mM). Reported to be more potent 

(IC 50 = 900 nM and 740 nM for Ab 40 and Ab 42 , respectively) in the 

presence of C99 inhibitor ( 0 mM). 

g-Secretase Inhibitor IX 565770 {DAPT; N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-Butyl 

Ester} 

A cell-permeable dipeptide that reduces Ab production by blocking 

g-secretase (Ab total IC 50 = 5 nM, Ab 42 IC 50 = 200 nM). Reported to be 

functionally active in both HEK293 cells and neuronal cultures without 

affecting the secretion of amyloid-b precursor protein. 

N InSolution g-Secretase Inhibitor IX 565784 {DAPT; N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-Butyl 

Ester} 

A 25 mM (5 mg/462 ml) solution of g-Secretase Inhibitor IX 


InSolution g-Secretase Inhibitor X 565771 {L-685,458; {1S-Benzyl-4R-[1-(1S-carbamoyl-2-phenethylcarbamoyl)- 

1S-3-methylbutylcarbamoyl]-2R-hydroxy-5-phenylpentyl}carbamic Acid 

tert-butyl Ester} 

g-Secretase Inhibitor XI 565772 

Supplied as a mM solution in 372 ml of DMSO. A cell-permeable, 

highly specific and potent inhibitor of g-secretase (Ab IC = 

total 50 

7 nM, Ab IC = 48 nM, and Ab IC = 67 nM in SH-SY5Y cells 

40 50 42 50 

overexpressing spbA4CTF). Binds to presenilin and blocks Notch 

intracellular domain production. Functions as a transition state analog 

mimic at the catalytic site of an aspartyl protease. Exhibits over 00fold 

greater selectivity for g-secretase than for cathepsin D. 

(7-Amino-4-chloro-3-methoxyisocoumarin; JLK6) 

A cell-permeable, active site-directed, irreversible serine protease 

inhibitor that acts as a highly selective, potent inhibitor of g-secretase. 

Blocks production of both amyloid-b (Ab ) and Ab < 00 mM in 

40 40 42 

HEK293 cells expressing wild-type and Swedish mutant b-amyloid 

precursor protein. 

g-Secretase Inhibitor XII 565773 (Z-IL-CHO) 

A cell-permeable, reversible dipeptide aldehyde that reduces Ab 

production by blocking g-secretase in vitro (Ab IC = 7.9 mM; 

40 50 

Ab IC = 7.6 mM) and in cultured CHO cells that stably overexpress 

42 50 

APP695 (Ab IC = .5 mM; Ab IC = 8.3 mM). Also blocks the 

40 50 42 50 

generation of g CTF (g-secretase-generated C-terminal fragment). 

Does not affect the formation of amyloid-b precursor protein. 

g-Secretase Inhibitor XIII 565774 (Z-YIL-CHO) 

A cell-permeable, reversible inhibitor of g-secretase. In TPA-stimulated 

T47- 4 cells, it abolished nuclear localization of ErbB-4 receptor 

tyrosine kinase by inhibiting the formation of the s80 ErbB-4 fragment. 

g-Secretase Inhibitor XIV 565775 [Z-Ct-Bu)-IL-CHO] 

A cell-permeable, reversible inhibitor of g-secretase that reduces Ab 

production (Ab IC = 90 nM; Ab IC = 780 nM) in solubilized 

40 50 42 50 

membrane preparations and in cultured APP695 expressing CHO cells 

(Ab IC = 80 nM; Ab IC = 20 nM). 

40 50 42 50 

g-Secretase Inhibitor XVI 565777 (DAPM; N-[N-3,5-Difluorophenacetyl]-L-alanyl-S-phenylglycine Methyl Ester) 

A cell-permeable g-secretase inhibitor with anti-aggregation property 

(Ab IC ~ 0 nM in 7PA2 cells). Prevents early Ab oligomerization by 

50 

selectively blocking the Ab dimer and trimer formation. 

InSolution g-Secretase Inhibitor 

XVII 

565778 (31C; WPE-III-31C) 

Supplied as a 5 mM (500 mg/ 56 ml) solution in DMSO. A cellpermeable 

(hydroxyethyl) urea peptidomimetic that acts as a 

transition-state analog inhibitor of g-secretase (IC 50 = 300 nM for Ab 

production in whole cells). Binds the presenilin-g-secretase complex 

(PS -NTF, PS -CTF, Nicastrin, and C83 APP CTF). 

mg $ 07 

5 mg $93 

5 mg $93 

250 mg $254 

5 mg $98 

5 mg $ 57 

5 mg $ 73 

5 mg $ 73 

5 mg $96 

500 mg $ 56 

02 Orders Phone 800 854 34 7 


Fax 800 776 0999 





InSolution g-Secretase Inhibitor 

XIX 

565787 {(2S,3R)-3-(3,4-Difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N- 

((3S)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyramide} 

Supplied as a 5 mM ( 00 mg/37 ml) solution in DMSO. A cell-permeable, 

highly potent g-secretase inhibitor (IC 50 = 60 pM towards Ab 40 

secretion in SH-SY5Y cells overexpressing spbA4CTF). 

N g-Secretase Inhibitor XX 565789 A cell-permeable, potent g-secretase inhibitor. Significantly lowers 

both the brain and plasma Ab 40 levels by ~72% in Tg2576 mutant APP 

transgenic mouse model ( 00 mM/kg, b.i.d.). Also potently inhibits 

Notch processing (IC 50 = .7 nM in SupT cells), and induces conversion 

of proliferative crypt cells into post-mitotic goblet cells in both 

C57BL/6 and APC Min mouse model ( 0 mM/kg, i.p.). 

N g-Secretase Inhibitor XXI 565790 A cell-permeable, potent, and selective peptidomimetic and nontransition-state 

analog inhibitor of g-secretase and Notch processing 

(IC 50 = 300 pM for Ab 40 in CHO cells overexpressing wild type bAPP; 

240 pM for Ab 40 , 370 pM Ab 42 and 320 pM for NICD, respectively, in 

HEK293 cells stably transfected with bAPP 695 and mNotchDE(M 727V); 

00 pM for both Ab 40 and Ab 42 in SH-SY5Y cells stably transfected 

with SPA4CT). Also lowers Ab levels in several APP transgenic mouse 

model. Reported to bind to presenilins and suppress the proteolytic 

ability to cleave several transmembrane protein substrates, including 

APLP and APLP2, CD44, ErbB4, E-cadherin, low density lipoprotein 

receptor-related proteins, Notch ligands, and p75 NTR . Yet, at higher 

concentrations (200-400 mM) only weakly affects presenilin activity. 

N 

Secretase Inhibitors, continued 

g -Secretase Inhibitor I 40 565765 [N-trans-3,5-Dimethoxycinnamoyl)-Ile-leucinal; t-3,5-DMC-IL-CHO] 

A potent, cell-permeable, reversible inhibitor of g-secretase that 

preferentially inhibits the secretion of Ab (>90%) vs. Ab (~ 5%). 

-40 -42 

IC = ~ 5 mM for Ab , ~22 mM for Ab , and >50 mM for Ab in 

50 total -40 -42 

CHO cells stably transfected with cDNA encoding bAPP695. Reported 

to be be about 0-fold more potent than Z-Val-Phe-CHO (MDL 28 70; 

Cat. No. 208722). 

g -Secretase Inhibitor II 40 565766 (N-tert-Butyloxycarbonyl-Gly-Val-Valinal) 

A cell-permeable, substrate-based (g -site) g-secretase inhibitor that 

40 

is reported to preferentially (> 90%) inhibit Ab cleavage at site 40 vs. 

42, in a dose-dependent fashion, in transiently transfected 293T cells 

over-expressing APP695NL. 


InnoZyme TACE Activity Kit 

The InnoZyme TACE Activity Kit is a specific and sensitive assay kit 

designed to measure human TACE activity in cell lysates and biological 

samples and for screening enzyme inhibitors. An anti-human TACE 

monoclonal antibody pre-coated on a 96-well plate captures human 

TACE. The activity of captured TACE is measured using an internally 

quenched fluorescent substrate, MCA-KPLGL-Dpa-AR-NH 2 . Cleavage 

of the scissile amide bond, G-L, releases the fluorophore from the 

quenching molecule, Dpa, resulting in an increase in fluorescence. 

The level of fluorescence is directly related to the enzyme activity. 

kit = 96 tests 

Cat. No. CBA042 1 kit $425 

00 mg $ 73 

500 mg $ 9 

500 mg $ 9 

mg $99 

mg 

5 mg 

$50 

$ 79 


Phone 800 628 8470 


03

Nitric Oxide/Oxidative Stress 


Arginase Inhibitors 

Arginase, an Mn 2+ metalloenzyme, catalyzes the 

hydrolysis of L-arginine to yield L-ornithine and urea 

in ureotelic animals. Based on their distribution, two 

isoforms of arginase have been described. Type I arginase, 

a cytosolic enzyme, is found in the hepatic tissue and 

besides participating in the urea cycle, it also plays 

a significant role in limiting the supply of arginine 

for nitric oxide (•NO) synthesis. Type II arginase is a 

mitochondrial enzyme found in extrahepatic tissues, and 

is involved in the regulation of extra-urea cycle arginine 

metabolism and in the down-regulation of NO synthesis. 

Arginase Inhibitors 


BEC, Hydrochloride 197900 [(S)-(2-Boronoethyl)-L-cysteine, HCI)] 

A slow-binding, competitive transition state inhibitor of arginase I 

and II (K i = 3 3 nM for human recombinant type II arginase). 

N G -Hydroxy-L-arginine, 

Monoacetate Salt 

N w -Hydroxy-nor-L-arginine, 

Diacetate Salt 

DL-a-Difluoromethylornithine, 

Hydrochloride 

399250 (NOHA, AcOH) 

A cell-permeable inhibitor of liver and macrophage arginase 

(K i = 50 mM). 

Due to the reciprocal regulation between arginase and 

nitric oxide synthase, arginase inhibitors are considered 

to have therapeutic potential in treating NO-dependent 

smooth muscle disorders, such as erectile dysfunctions 

and polyamine induced bronchial constriction. 

References: 

Colleluori, D.M., and Ash, D.E. 200 . Biochemistry 40, 9356. 

Ozaki, M., et al. 999. J. Biochem. 125, 586. 

Salimuddin et al. 999. Am J. Physiol. Endocrinol. Metab. 277, E 0. 

Morris, S.M. Jr., et al. 998. Am J. Physiol. Endocrinol. Metab. 275, E740. 

More online... www.calbiochem.com/inhibitors/arginase 

399275 [L-2-Amino-(4-(2´-hydroxyguanidino)butyric Acid, 2CH 3 CO 2 H; nor-NOHA, 

2CH 3 CO 2 H] 

A potent, selective, competitive, and high affinity inhibitor of arginase 

(IC 50 = 2 mM for rat liver arginase). 

288500 (DFMO; Eflornithine; RMI-71782) 

An arginase inhibitor that potentiates vasodilatory effects of adenosine 

and also acts as an irreversible inhibitor of ornithine decarboxylase. 

5 mg $ 40 

5 mg $87 

04 Orders Phone 800 854 34 7 


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mg 

5 mg 

$34 

$83 

25 mg $70

Glutathione S-Transferase (GST) Inhibitors 

Glutathione S-transferases (GSTs) constitute a family 

of phase II detoxification isozymes that catalyze 

the conjugation of glutathione with a number of 

hydrophobic compounds. Due to high expression of GSTs 

in tumors compared to normal tissues and their high 

level in plasma from cancer patients, these enzymes 

are considered to be cancer markers. All species 

possess multiple cytosolic and membrane-bound GST 

isozymes. These isozymes differ in their tissue-specific 

expression and distribution. They provide protection to 

mammalian cells against the toxic and neoplastic effects 

of electrophilic metabolites of carcinogens and reactive 

oxygen species. Increased expression of GST isozymes 

Glutathione S-Transferase Inhibitors 



has been linked to the development of resistance to 

alkylating cytostatic drugs. Their deficiency reportedly 

increases predisposition to various forms of cancer. 

Hence, GST status may be a useful prognostic factor to 

determine the clinical outcome of chemotherapy. 

References: 

Wu, Z., et al. 2004. J. Med. Chem. 47, 3282. 

Dirven, H.A., et al. 995. Chem. Res. Toxicol. 8, 979. 

Kolm, R.H., et al. 995. Biochem. J. 311, 453. 

Cameron, A.D., et al. 995. Structure 3, 7 7 

Talalay, P., et al. 995. Toxicol. Lett. 82-83, 73. 

More online... www.calbiochem.com/inhibitors/GST 



An effective, irreversible inhibitor of glutathione S-transferases and a 

non-competitive inhibitor of xanthine oxidase. Also acts as a selective, 

non-competitive inhibitor of 5-lipoxygenase (ID 50 = 3.7 uM). 

Luteolin 440025 (3´,4´,5,7-Tetrahydroxyflavone) 

An antioxidant flavonoid and a free radical scavenger that is shown to 

inhibit rat liver cytosolic glutathione S-transferase activity. 

Sulfasalazine 573500 A cell-permeable anti-inflammatory agent that acts as an inhibitor 

of glutathione-S-transferase (IC 50 = 0 mM in HG9 cell line). Strongly 

inhibits NF-kB activation and potently induces apoptosis in Tlymphocytes. 

Causes neutrophil apoptosis that can be abrogated by 

tyrosine kinase inhibitors, protein kinase A inhibitors, or antioxidants. 

Also inhibits basic fibroblast growth factor-induced endothelial cell 

chemotaxis. 

500 mg $48 

5 mg $58 

00 mg $33 


Phone 800 628 8470 


05


Guanylate Cyclase (GC) Inhibitors 

Guanylyl cyclase (GC) catalyzes the formation of the 

second messenger cyclic GMP (cGMP) from GTP and 

exists in both the soluble and particulate fractions. The 

soluble enzyme can be regulated by free radicals and 

nitrovasodialators, whereas the particulate enzyme can 

be regulated by various peptides. cGMP signaling is 

mediated by cGMP-activated protein kinases, the cGMPregulated 

phosphodiesterases and the cGMP-gated ion 

channels. The action of cGMP is terminated by the action 

of cGMP-degrading phosphodiesterases. GC is present 

either as soluble (sGC) or as membrane-bound enzyme 

linked to a receptor. sGC is activated by another second 

messenger, nitric oxide (NO). Membrane-bound GC, on 

the other hand, is activated by hormones. The prosthetic 

heme group of sGC acts as the NO sensor, and binding of 

NO induces conformational changes leading to an up to 

200-fold activation of the enzyme. The organic nitrates 

commonly used in the therapy of coronary heart disease 

exert their effects via stimulation of this enzyme. Two 

isoforms of the NO-sensitive heterodimeric enzyme have 

been identified, the ubiquitous a1b1 isoform and the less 

broadly distributed a2b1 isoform. These two forms differ 

in their subcellular distribution. 

Membrane-bound GCs are receptor-linked enzymes with 

one membrane-spanning region. Although all of these 

GCs share a conserved intracellular catalytic domain, 

they differ in their extracellular ligand-binding domains 

and are activated by different peptide hormones. 

Guanylate Cyclase Inhibitors 

The guanylyl cyclase A (GC-A) isoform acts as the 

receptor for the natriuretic peptides, ANP and BNP, 

and hormones that are involved in the regulation of 

blood pressure as well as in the water and electrolyte 

household. GC-B is mainly found in the vascular 

endothelium and is thought to participate in smooth 

muscle relaxation. It displays the highest affinity for the 

natriuretic peptide of the C-type (CNP). GC-C is reported 

to bind the peptide hormone guanylin found in the 

intestine, where it is involved in salt and water balance. 

GC-C is stimulated by the heat-stable enterotoxin 

produced by E. coli. 

References: 

Friebe, A., and Koesling, D. 2003. Cir. Res. 93, 96. 

Denninger, J.W., and Marletta M.A. 999. Biochim. Biophys. Acta 1411, 334. 

Russwurm, M., and Koesling, D. 2002. Mol. Cell Biochem. 230, 59. 

Koesling, D., and Friebe, A. 999. Rev. Physiol. Biochem. Pharmacol. 135, 35. 

More online... www.calbiochem.com/inhibitors/GCI 


LY 83583 440205 (6-Anilino-5,8-quinolinequinone) 

A cell-permeable, competitive inhibitor of soluble guanylate cyclase 

(IC 50 = 2 mM). Lowers the production of cGMP levels in a wide range of 

tissues by blocking intracellular Ca 2+ release, with negligible effect on 

cAMP levels. Inhibits nitric oxide-induced smooth muscle relaxation. 

Methylene Blue 457250 [3,7-bis(Dimethylamino)phenothiazin-5-ium Chloride] 

An inhibitor of soluble guanylate cyclase that acts as an organic spintrap. 

Forms stable adducts with oxygen free radicals in solution. 

NS 2028 492030 [4H-8-Bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] 

A potent, specific, and irreversible inhibitor of soluble guanylyl cyclase 

(IC 50 = 30 nM for basal and 200 nM for NO-stimulated enzyme activity; 

IC 50 = 7 nM for S-nitrosoglutathione-enhanced soluble guanylyl 

cyclase activity in homogenates of mouse cerebellum). 

ODQ 495320 (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one) 

A cell-permeable, potent and selective inhibitor of nitric oxide (NO)sensitive 

soluble guanylyl cyclase (IC 50 = 20 nM). In cerebellum slices, 

ODQ is shown to reversibly inhibit the NO-dependent cGMP response to 

glutamate receptor agonists without affecting NOS activity. 

06 Orders Phone 800 854 34 7 


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5 mg 

25 mg 

$69 

$263 

g $33 

5 mg $ 50 

0 mg $ 27

Guanylate Cyclase Inhibitors, continued 




Zinc (II) Protoporphyrin IX 691550 (ZnPP-9) 

A potent and selective inhibitor of heme oxygenase, the enzyme 

generates carbon monoxide (CO) and biliverdin. Inhibits 

soluble guanylyl cyclase and produces a time- and concentrationdependent 

inactivation of all three isoforms of nitric oxide synthase 

(IC = 800 nM, 4.0 mM, and 5.0 mM for nNOS, iNOS, and eNOS, 

50 

respectively). Inhibits relaxation induced by acetylcholine, ANP, and 

VIP in isolated rat aorta. Blocks interleukin- and prevents induction 

of long-term potentiation. Also useful as an indicator of iron-deficient 

erythropoiesis. Does not cross the blood-brain barrier. 

25 mg $53 


Phone 800 628 8470 


07


Nitric Oxide Synthase (iNOS, bNOS, eNOS) Inhibitors 

Nitric oxide (•NO), a highly reactive, diffusible, 

and unstable radical, plays an important role in 

the regulation of a wide range of physiological 

processes, including cellular immunity, angiogenesis, 

neurotransmission, and platelet aggregation. •NO is 

synthesized from L-arginine by the action of nitric 

oxide synthase (NOS) in a two-step oxidation process. 

Free •NO is a transient species with a half-life of only 

about five seconds. Hence, most studies on •NO action 

are based on the activity of NOS. •NO can diffuse 

across the cell membrane and react with a variety of 

targets. Reaction of •NO with O 2 in aqueous solutions 

produces the relatively unreactive nitrate and nitrite 

ions as products. However, •NO can rapidly react with 

superoxide to produce highly reactive peroxynitrite 

(ONOO - ). Almost all biological effects of •NO are 

achieved either directly or through other reactive 

nitrogen intermediates. 

NOS is known to exist in three isoforms: (a) a soluble 

constitutively expressed enzyme found in high 

concentrations in the brain (bNOS, nNOS, or NOS-1), 

(b) a constitutively expressed endothelial membrane 

bound enzyme (eNOS or NOS-3), and (c) an inducible 

enzyme (iNOS or NOS-2) that is associated with the 

cytotoxic function of macrophages. These enzymes 

exist as homodimers, each monomer consisting of two 

major domains: an N-terminal oxygenase domain 

and a C-terminal reductase domain. The interdomain 

linker contains the calmodulin-binding sequence. These 

three isoforms exhibit similarities in their structure 

and mechanism of action. Calmodulin is required for 

the activity of all three isoforms. The activation of 

the constitutively expressed isoforms requires Ca 2+ - 

dependent binding of calmodulin to the enzyme. 

However, in the case of iNOS, calmodulin is irreversibly 

bound to the enzyme and its activity is regulated by 

its rate of synthesis rather than by Ca 2+ concentration. 

In the absence of calmodulin iNOS is highly unstable. 

For their catalytic activities NOS isoforms require 

three distinct domains: (a) a reductase domain, (b) a 

calmodulin-binding domain, and (c) an oxygenase 

domain. The reductase domain contains the FAD and 

FMN moieties. The oxygenase domain, which contains 

the binding sites for heme, tetrahydrobiopterin, and 

arginine, catalyzes the conversion of L-arginine to 

citrulline and •NO. The maximal rate of •NO synthesis 

is established by the intrinsic maximum ability of 

the reductase domain to deliver electrons to the heme 

domain. 

Because of the involvement of all the three NOS 

isozymes in various aspects of signal transduction, NOS 

inhibitors have gained prominence in the management 

of ischemic reperfusion injury, hypotensive effects of 

drugs, and inflammatory response to cytokines. 

References: 

Achike, F.I., and Kwan, C.Y. 2003. Clin. Exp. Pharmacol. Physiol. 30, 605. 

Chu, C.J., et al. 2000. Clin. Sci. 99, 475. 

Mori. M., and Gotoh, T. 2000. Biochem. Biophys. Res. Commun. 275, 7 5. 

Wang, Y. et al. 999. Crit. Rev. Neurobiol. 13, 2 . 

Stuehr, D.J. 999. Biochim. Biophys. Acta 1411, 2 7. 

Moncada, S. 999. J. R. Soc. Med. 92, 64. 

Michel, T. 999. Braz. J. Med. Biol. Res. 32, 36 . 

Jaffrey, S.R., and Snyder, S.H. 996. Science 274, 774. 

More online... www.calbiochem.com/inhibitors/NOS 

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Characteristics of various forms of Nitric Oxide Synthases 



Enzyme Gene Number of Residues Cellular Localization and Expression Regulation 

nNOS NOS1 429- 433 Brain: mainly soluble skeletal muscle: mainly particulate Ca 2+ /CaM 

iNOS NOS2 44- 53 Variety of cells: mainly soluble Cytokine-inducible 

Ca 2+ -independent 

eNOS NOS3 203- 205 Vascular endothelial cells and cardiomyocytes: mainly 

particulate 

Biological Activities of Selected Nitric Oxide Synthase Inhibitors (IC 50 values in mM) 

Product Cat. No. eNOS iNOS bNOS 

400W 00050 50* 0.007* 2* 

Aminoguanidine, Hemisulfate 54500 526 250 

-Amino-2-hydroxyguanidine, 

p-Toluensulfate 

55200 68 

Bromocriptine Mesylate 203850 > 00 0 

Dexamethasone 265005 0.005 

N G ,N G -Dimethyl-L-arginine, 


N G ,N G ’-Dimethyl-L-arginine, 


3 203 

3 204 

Diphenyleneiodonium Chloride 300260 0. 8 0.05 

2-Ethyl-2-thiopseudourea, 

Hydrobromide 

34 80 0.036 † 0.0 7 † 0.029 † 

Haloperidol 37 980 3 † 

L-N 5 -( -Iminoethyl)ornithine, 


MEG, Hydrochloride 444600 

400600 0.5 2.2 3.9 

S-Methylisothiourea Sulfate (SMT) 466220 2.0 ‡ 

S-Methyl-L-thiocitrulline, 


N G -Monoethyl-L-arginine, 


472804 5.4 34 0.3 

475883 8 

Interested in Oxidative Stress Kits? 

Visit our website 

www.calbiochem/stresskits 

Ca 2+ /CaM 

Product Cat. No. eNOS iNOS bNOS 

N G -Monomethyl-D-arginine, 


N G -Monomethyl-L-arginine, 

Monoacetate (L-NMMA) 

N G -Nitro-L-arginine Methyl Ester, 

Hydrochloride 

475892 

475886 0.7 3.9 0.65 

483 25 0.5 

L-NIL, Dihydrochloride 482 00 3.3 92 

N G -Nitro-L-arginine (L-NNA) 483 20 0.09 † 8. † 0.025 † 

7-Nitroindazole 483400 0.8 20 0.7 

7-Nitroindazole, Sodium Salt 484500 

7-Nitroindazole, 3-Bromo- 2039 0.29 0.86 0. 7 

7-Nitroindazole, 3-Bromo-, Sodium Salt 2039 2 

Abbreviations: bNOS: brain nitric oxide synthase; eNOS: endothelial nitric oxide synthase; iNOS: inducible nitric oxide synthase. 

Note: *: K d ; †:K i ; ‡: EC 50 

nNOS Inhibitor I 490070 3 4 † 39 † 0. 2 † 

,3-PBITU, Dihydrobromide 5 2774 9 † 0.047 † 0.25 † 

L-Thiocitrulline, Dihydrochloride 5894 3.6 † 0.06 † 

N G -Propyl-L-arginine 537200 8.5 80 0.057 

SKF-525A, Hydrochloride 567300 90 

TRIM 643500 > 000 27 28.2 


Phone 800 628 8470 


09


Nitric Oxide Synthase (NOS) Inhibitors 


400W 100050 [N-(3-Aminomethyl)benzylacetamidine, 2HCl] 

A cell-permeable, selective, irreversible, slow, tight binding inhibitor of 

iNOS (K d = 7 nM) both in vitro and in vivo. 

400W, Immobilized 100051 An immobilized form of the iNOS inhibitor (Cat. No. 00050) covalently 

attached to hydrophilic acrylic beads via an 8-carbon spacer. Useful to 

affinity-precipitate NOS and other functionally related proteins from 

cell lysates and tissue extracts. 

Aminoguanidine, Hemisulfate 154500 An irreversible inhibitor of both constitutive (IC 50 = 526 mM) and 

inducible (IC 50 = 250 mM) NOS activity in homogenates of rat ileal and 

colonic tissue. 


p-Toluenesulfonate 

155200 A potent, cell-permeable, inhibitor of iNOS in murine macrophages (IC 50 

= 68 mM) and rat aortic smooth muscle cells (RASM) in culture (IC 50 = 

4 mM). 

Bromocriptine Mesylate 203850 (BCT; BRC; 2-Bromo-a-ergocryptine, Methanesulfonate) 

Selectively inhibits neuronal NOS (nNOS; IC 50 = 0 mM) by affecting the 

activation of NOS by calmodulin. Has only a weak inhibitory effect on 

inducible NOS (iNOS; IC 50 > 00 mM). 

Chlorpromazine, Hydrochloride 215921 {2-Chloro-10-[3´-(dimethylamino)propyl]phenothiazine, HCl} 

Inhibits NOS in mouse brain. 

Dexamethasone 265005 (9a-Fluoro-16a-methylprednisolone) 

Inhibits the expression of inducible, but not constitutive NOS in 

vascular endothelial cells (IC 50 = 5 nM). 

N G ,N G -Dimethyl-L-arginine, 


N G ,N G´ -Dimethyl-L-arginine, 


Diphenyleneiodonium Chloride 300260 (DPI) 

2-Ethyl-2-thiopseudourea, 

Hydrobromide 

311203 (ADMA, 2HCl) 

A cell-permeable, reversible inhibitor of NOS in vitro (IC 50 = 2-3 mM) 

and in vivo. 

311204 (SDMA, 2HCl) 

A cell-permeable and endogenous reversible inhibitor of nitric oxide 

synthesis in vitro and in vivo. 

An irreversible, cell-permeable, inhibitor of eNOS (IC 50 = 5 nM in 

macrophages). 

341180 (S-Ethyl-ITU, HBr; S-Ethylisothiourea, HBr) 

A highly potent, cell-permeable, competitive inhibitor of human 

inducible (K i = 7 nM), endothelial (K i = 36 nM), and neuronal 

(K i =29 nM) NOS isozymes. 

5 mg $ 00 

set $ 32 

00 mg $37 

0 mg $98 

25 mg $48 

500 mg $57 

00 mg $62 

25 mg $ 00 

25 mg $60 

0 mg $62 

00 mg $34 

Haloperidol 371980 Acts as a non-competitive inhibitor of porcine bNOS activity (K i = 3 mM). 00 mg $27 

L-N 5 -( -Iminoethyl)ornithine, 


400600 (L-NIO, 2HCl) 

A potent, cell-permeable, inhibitor of eNOS (IC 50 = 500 nM). 

MEG, Hydrochloride 444600 (Mercaptoethylguanidine, HCl) 

A cell-permeable inhibitor of iNOS and a peroxynitrite scavenger. 

Melatonin 444300 (N-Acetyl-5-methoxytryptamine; 5-Methoxy-N-acetyltryptamine) 

Inhibits rat cerebellar NOS. Also acts as a peroxynitrite scavenger. 

S-Methyl-L-thiocitrulline, 


472804 [N d -(S-Methyl)isothioureido-L-ornithine] 

A cell-permeable, inhibitor of NOS that exhibits about 7-fold greater 

selectivity for rat nNOS (IC 50 = 300 nM) compared to the eNOS (IC 50 = 

5.4 mM). 

S-Methylisothiourea, Sulfate 466220 (2-Methyl-2-thiopseudourea, Sulfate; SMT) 

A cell-permeable, highly selective inhibitor of iNOS. Reported to be 

0–30 fold more potent than L-NMMA (Cat. No. 475886) as an inhibitor 

of iNOS in immunostimulated cultured macrophages (EC 50 = 6 mM) and 

vascular smooth muscle cells (EC 50 = 2 mM). 

N G -Monoethyl-L-arginine, 


N G -Monomethyl-D-arginine, 


475883 (NMEA, AcOH) 

A cell-permeable inhibitor of nitric oxide synthase (NOS) (K i = 8 mM 

for iNOS; K i = 66 mM for cNOS). 

475892 (N G -Me-D-Arg, AcOH; N w -Me-D-Arg; D-NMMA) 

A cell-permeable, negative control for N G -Monomethyl-L-arginine (Cat. 

No. 475886). May be used to investigate non-specific L-NMMA activity. 

Does not have any significant effect on nitric oxide synthase. 

20 mg $92 

0 mg $7 

g $45 

0 mg $ 22 

00 mg $38 

0 mg $48 

0 Orders Phone 800 854 34 7 


Fax 800 776 0999 


0 mg 

25 mg 

00 mg 

$49 

$95 

$2 0

Nitric Oxide Synthase (NOS) Inhibitors, continued 




N G -Monomethyl-L-arginine, 


475886 (N w -Me-L-Arg; N G -Me-L-Arg, AcOH; L-NMMA) 

A cell-permeable, L-arginine analog that acts as a competitive inhibitor 

of all three isoforms of NOS (IC 50 = 650 nM for nNOS; IC 50 = 700 nM for 

eNOS; IC 50 = 3.9 mM for iNOS). 

L-NIL, Dihydrochloride 482100 [L-N 6 -(1-Iminoethyl)lysine, DiHCl] 

A potent, cell-permeable, and selective NOS inhibitor that exhibits 

greater selectivity for iNOS (IC 50 = 3.3 mM) compared to nNOS (IC 50 = 

92 mM). 

nNOS Inhibitor I 490070 {(4S)-N-(4-Amino-5[aminoethyl]aminopentyl)-N´-nitroguanidine, TFA} 

A potent, cell-permeable, and highly selective inhibitor of nNOS (K i = 

20 nM). Displays >2500-fold and 92-fold selectivity over eNOS and 

iNOS, respectively. 

N G -Nitro-L-arginine 483120 (L-NNA; N G -NO 2 -L-Arg) 

A potent, cell-permeable, reversible inhibitor of bNOS (K i = 25 nM) and 

eNOS (K i = 90 nM). 

N G -Nitro-L-arginine Methyl Ester, 

Hydrochloride 

483125 (L-NAME, HCl; N w -NO 2 -L-Arg-OMe; N G -NO 2 -L-Arg-OMe) 

A cell-permeable, more soluble analog of arginine and a competitive, 

slowly reversible inhibitor of eNOS (IC 50 = 500 nM). 

p-Nitroblue Tetrazolium Chloride 484235 (NBT; Nitro BT) 

NADPH-diaphorase substrate that competitively inhibits NOS 

(IC 50 = 3–4 mM). 

7-Nitroindazole 483400 (7-Ni) 

7-Nitroindazole, Sodium Salt 484500 (7-NiNa) 

7-Nitroindazole, 3-Bromo-, 

Sodium Salt 

A cell-permeable, reversible and competitive inhibitor of nitric oxide 

synthase (NOS) with high selectivity for the bNOS (IC 50 = 7 0 nM). Also 

inhibits bovine eNOS (IC 50 = 800 nM). Binds to the heme group of NOS. 

A more soluble form of 7-Nitroindazole (Cat. No. 483400). Its solubility 

in artificial cerebrospinal fluid permits its use as an inhibitor of NOS in 

brain tissue. 

203912 (BrNINa) 

Sodium salt of 3-Bromo-7-Nitroindazole (Cat. No. 2039 ) that is more 

soluble in aqueous solutions and still penetrates the brain. 

,3-PBITU, Dihydrobromide 512774 [S,S´-1,3-Phenylene-bis(1,2-ethanediyl)-bis-isothiourea, 2HBr] 

A highly potent, cell-permeable, competitive inhibitor of human nitric 

oxide synthase. Exhibits approximately 200 fold higher selectivity for 

iNOS (K i = 47 nM) compared to eNOS (K i = 9.0 mM). 

PPM- 8 529570 (2-Benzoylamino-1,4-naphthoquinone) 

A novel, cell-permeable, anti-inflammatory agent that inhibits the 

expression of inducible nitric oxide synthase (iNOS; IC 50 ~5 mM). 

Acts by blocking the activation of NF-kB in vitro and in vivo. 

N G -Propyl-L-arginine 537200 (N-PLA; N w -Propyl-L-arginine) 

A potent, cell-permeable, competitive, and time-dependent inhibitor 

of nNOS (K i = 57 nM for nNOS; K i = 80 mM for iNOS; K i = 8.5 mM for 

eNOS). 

-Pyrrolidinecarbodithioic Acid, 

Ammonium Salt 

548000 (Ammonium Pyrrolidinedithiocarbamate; APDC; PDTC, NH 4 ) 

A cell-permeable inhibitor of inducible NOS inhibits the induction of 

nitric oxide synthase activity in rat alveolar macrophages. 

SKF-525A, Hydrochloride 567300 (Proadifen) 

A cell-permeable inhibitor of neuronal nitric oxide synthase 

(IC = 90 mM). 

50 

L-Thiocitrulline, Dihydrochloride 589411 (2-Thioureido-L-norvaline) 

A potent, cell-permeable, inhibitor of nNOS (K i = 60 nM) compared to 

iNOS (K i = 3.6 mM). 

TRIM 643500 [1-(2-Trifluoromethylphenyl)imidazole] 

A potent, cell-permeable, inhibitor of nNOS (IC 50 = 28.2 mM) and iNOS 

(IC 50 = 27.0 mM), however, it is only a weak inhibitor of eNOS 

(IC 50 = .06 mM). 

25 mg 

50 mg 

00 mg 

$65 

$ 4 

$2 0 

0 mg $ 7 

mg 

5 mg 

$70 

$2 

00 mg $33 

00 mg $33 

250 mg 

g 

$37 

$ 29 

00 mg $83 

0 mg $48 

0 mg $98 

50 mg $8 

0 mg $98 

5 mg $75 

00 mg $34 

g $2 5 

0 mg $ 07 

00 mg $48 


Phone 800 628 8470 



Nitric Oxide Synthase, Inducible, Inhibitor Set 

(iNOS Inhibitor Set) 

Provided as a 5 vial set. Each set contains 5 mg of 400W (Cat. No. 

00050); 0 mg of -Amino-2-hydroxyguanidine, p-Toluenesulfonate 

(Cat. No. 55200); 00 mg of S-Methylisothiourea Sulfate (Cat. No. 

466220); 0 mg of L-NIL, Dihydrochloride (Cat. No. 482 00); and 50 mg 

of ,3-PBITU, Dihydrobromide (Cat. No. 5 2774). 

Cat. No. 482760 1 set $340 


Nitric Oxide Assay Kit, Colorimetric 

Assay kit for the rapid quantitative measurement of total nitric oxide 

(NO). Based on the enzymatic conversion of nitrate to nitrite by nitrate 

reductase, followed by the spectrophotometric quantitation of nitrite 

levels using Griess Reagent. Do not use with nitrate- or nitritecontaining 

tissue culture media such as RPMI. kit = 50 tests. 

Cat. No. 482650 1 kit $286 

Nitric Oxide Assay Kit, Fluorometric 

Assay kit useful for the rapid quantitative measurement of nitric oxide 

(NO). Displays 50-fold increased sensitivity over the colorimetric nitric 

oxide assay kit (Cat. No. 482650). The assay is based on the enzymatic 

conversion of nitrate to nitrite by nitrate reductase, followed by the 

addition of 2,3-diaminonapthalene (DAN), and NaOH, which converts 

nitrite to a fluorescent compound. Fluorescence measurements of 

- this compound accurately determine the nitrite (NO ) concentration 

2 

(excitation max.: 365 nm; emission max.: 450 nm). Do not use with 

nitrate- or nitrite-containing tissue culture media such as RPMI. 

kit = 80 tests. 

Cat. No. 482655 1 kit $286 

NOS Inhibitor Set 

Contains 20 mg of L-N 5 -( -Iminoethyl)ornithine, HCl (Cat. No. 

400600), 0 mg of S-Methyl-L-thiocitrulline, HCl (Cat. No. 472804), 

25 mg of N G -Monomethyl-L-arginine, Monoacetate Salt (Cat. No. 

475886), 00 mg of N G -Nitro-L-arginine Methyl Ester, HCl (Cat. No. 

483 25), 00 mg of N G -Nitro-D-arginine Methyl Ester, HCl, 00 mg of 

7-Nitroindazole (Cat. No. 483400), and 0 mg of L-Thiocitrulline, HCl 

(Cat. No. 5894 ). 

Cat. No. 490075 1 set $380 

Nitric Oxide Synthase Assay Kit 

Assay kit useful for the rapid quantitative measurement of nitric oxide 

synthase (NOS) activity. It is based on the conversion of radioactive 

L-arginine to L-citrulline by NOS. Radioactive citrulline is separated 

from unreacted arginine on a cation-exchange resin and quantitated. 

kit = 50 tests. 

Cat. No. 482700 1 kit $329 

Nitric Oxide Synthase Assay Kit, Colorimetric 

Assay kit useful for the rapid and accurate measurement of nitric 

oxide synthase (NOS) activity. This colorimetric assay uses lactate 

dehydrogenase (LDH) to destroy excess NADPH (cofactor for NOS) 

which interferes with the chemistry of Griess Reagent, commonly used 

for nitrite/nitrate detection. Do not use with nitrate- or nitritecontaining 

tissue culture media such as RPMI. kit = 96 tests. 

Cat. No. 482702 1 kit $286 

2 Orders Phone 800 854 34 7 


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Proteases 

Anthrax Lethal Factor (LF) Metalloprotease Inhibitors 


Proteases 


Anthrax Lethal Factor Protease 176901 [Anthrax LF Protease Inhibitor; Bacillus anthracis LF Protease Inhibitor; 

mg $ 95 

Inhibitor, In-2-LF 

In-2-LF] 

N Anthrax Lethal Factor Protease 


More online... www.calbiochem.com/inhibitors/ALF 

A cell-permeable N-acetylated, C-hydroxamate derivative of a 4-mer 

peptide designed from the MEK-2 template that acts as a competitive 

inhibitor of anthrax lethal factor (LF) metalloprotease (K = nM). 

i 

Also inhibits MEK-3 cleavage. Protects against anthrax toxin induced 

cytotoxicity in RAW264.7 and J772.A cells. 

176910 [BI-11B3; 5-(5-(2-Chloro-5-trifluoromethyl-phenyl)-furan-2ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl)-acetic 

acid] 

A cell-permeable, rhodanine-acetic acid analog that chelates the 

active site Zn2+ and acts as a potent inhibitor of anthrax lethal factor 

(LF) metalloproteinase (K = 32 nM). Exhibits only minimal inhibition of 

i 

MMP-2 and MMP-9. Shown to effectively prevent LF-induced MAPKK 

proteolysis (< 2 mM) and offer protection against LF and protective 

antigen (PA) cytotoxic effects in RAW264.7 cells (IC < 5 mM). In 

50 

combination with the antibiotic ciprofloxacin, doubly enhances the 

survival rates of mice challenged with anthrax spores. 

5 mg $ 29 


Phone 800 628 8470 


3

Proteases 

Calpain Inhibitors 

Calpains belong to a family of calcium-dependent thiolproteases 

that proteolyze a wide variety of cytoskeletal, 

membrane-associated, and regulatory proteins. Fifteen 

gene products of the calpain family are reported in 

mammals, which are classified as nine typical and six 

atypical calpains. Typical calpains are characterized 

by a C-terminal Ca 2+ -binding domain that includes EFhand 

motifs, while atypical calpains lack this region, 

but often contain additional domains. Calpains do not 

generally function as destructive proteases, but act as 

calcium-dependent modulators that remove limited 

portions of protein substrates. Calpains respond to 

Ca 2+ signals by cleaving specific proteins, frequently 

components of signaling cascades, thereby irreversibly 

modifying their function. Two major isoforms of calpain 

are reported in mammals, calpain-1 (m-form) and 

calpain-2 (m-form). They are constitutively expressed 

in all tissues and differ in their calcium requirement 

for activation (~50 mM for calpain-1 and ~500 mM for 

calpain-2) and contain several calcium-binding sites, 

which allosterically affect the enzyme activity. 

Calpain-1 and -2 exhibit about 55-65% sequence 

homology and are composed of an 80 kDa and a 30 kDa 

subunit. The 80 kDa subunit has the catalytic site and 

is unique to each isozyme, whereas the 30 kDa unit is 

the regulatory subunit and is common to both calpain- 

1 and -2. The 80 kDa subunit consists of four domains 

(I-IV) and the 30 kDa unit has 2 domains (V and VI). 

Domain I is partially removed during autolysis. Domain 

II is the protease domain, which is structurally similar 

to the catalytic domain of other cysteine proteases. It 

contains a Cys-His-Asn triad characteristic of cysteine 

proteases. Domain III exhibits a homology with typical 

calmodulin binding proteins and interacts with calcium 

binding domains (IV and VI) and frees domain II for 

protease activity. Domain IV is a Ca 2+ -binding domain 

structurally similar to calmodulin. Domain V contains 

a hydrophobic region and is essential for calpain 

interaction with membranes. Domain VI has five EFhands. 

There are two EF-hand pairs, one pair (EF1-EF2) 

displays an ‘open’ conformation and the other (EF3-EF4) 

a ‘closed’ conformation. The fifth EF-hand (EF5) is in a 

‘closed’ conformation. Both, calpain-1 and -2 associate 

non-covalently with domain V and domain VI. Several 

putative substrates of calpain-1 and -2 are known 

that are cleaved by both isoforms, but with different 

efficiencies. Recently, determinants for calpain-1 and 

-2 have been analyzed and it is shown that amino acid 

preferences extend over 11 residues around the scissile 

bond. Calpains prefer Leu, Thr, Val in the P2 position, 

Lys, Tyr, Arg in the P1 position, and proline in the region 

flanking the P2 - P’1 segment. 

Calpain-3, another typical calpain was first described 

as a skeletal muscle-specific calpain isoform. However, 

subsequent studies have shown its presence in several 

other tissues. It is a 94 kDa enzyme that contains 

821 amino acids. Structurally calpain-3 is similar 

to calpain-1 and -2, however, it has an additional Nterminal 

sequence of 20-30 amino acids (NS). Also, its 

domain I exhibits less than 20% homology to calpain-1 

and -2. Calpain-3 includes two characteristic amino 

acid stretches: one between the catalytic cysteine 

and histidine (IS1) and the other (IS2) upstream of the 

first EF hand motif of calcium-binding domain IV. 

A characteristic feature of calpain 3 is that it is not 

inhibited by calpastatin. While conventional calpains 

localize mainly in the cytosol or at the inner face of 

the plasma membrane, calpain-3 is detected within the 

nuclei of skeletal muscle cells and in the N2 region of 

myofibrils. 

More recently, attention has been focused on the 

pathological significance of calcium accumulation in 

the central nervous system following cerebral ischemia 

and traumatic brain injury. Overactivation of NMDA, 

kainate, and AMPA receptors in the brain leads to 

sustained influx of Ca 2+ through the voltage-gated 

calcium channels. Disturbances in calcium homeostasis 

result in the activation of several calcium-dependent 

enzymes including calpains. Overexpression of calpains 

has been positively linked to both acute and chronic 

neurodegenerative processes including ischemia, 

trauma, and Alzheimer’s disease. In Alzheimer’s disease 

4 Orders Phone 800 854 34 7 


Fax 800 776 0999 


the ratio of active (76 kDa) to inactive (80 kDa) calpain- 

1 is reported to be much higher than normal. Calpain 

proteolysis is usually the late-stage common pathway 

towards cell death induced by excitotoxic compounds; 

hence, a selective inhibition of calpains to limit neuronal 

damage appears to be a viable therapeutic measure. 

However, most of the inhibitors reported are active site 

targeted peptides and their limited cell permeability 

poses problems. PD 150606 (Cat. No. 513022), a cellpermeable 

inhibitor for calpains, may serve as a useful 

tool for these studies. 

Calpain Inhibitors 


Proteases 


ALLM 208721 (Calpain Inhibitor II) 

A cell-permeable inhibitor of calpain I (K i = 20 nM), calpain II (K i = 

230 nM), cathepsin B (K i = 00 nM), and cathepsin L (K i = 600 pM). 

ALLN 208719 (Calpain Inhibitor I; LLNL; MG 101) 

A cell-permeable inhibitor of calpain I (K i = 90 nM), calpain II (K i = 

220 nM), cathepsin B (K i = 50 nM), and cathepsin K (K i = 500 pM). 

InSolution ALLN 208750 (Calpain Inhibitor I; LLNL; MG 101) 

A 0 mM (5 mg / .3 ml) solution of ALLN (Cat. No. 2087 9) in DMSO. 

Calpain Inhibitor III 208722 (Carbobenzoxy-valinyl-phenylalaninal; MDL 28170) 

A potent, cell-permeable inhibitor of calpain I and II (K i = 8 nM). 

Calpain Inhibitor IV 208724 (Z-LLY-FMK) 

A potent, cell-permeable, and irreversible inhibitor of calpain II 

(k 2 = 28,900 M - s - ). 

Calpain Inhibitor V 208726 (Mu-Val-HPh-FMK) 

A potent, non-selective, cell-permeable, and irreversible inhibitor of 

calpain (~ 00 mM). 

Calpain Inhibitor VI 208745 [N-(4-Fluorophenylsulfonyl)-L-valyl-L-leucinal; SJA6017] 

A cell-permeable, potent, and reversible inhibitor of calpain I 

(IC = 7.5 nM) and calpain II (IC = 78 nM). 

50 50 

Calpain Inhibitor X 208742 (Z-L-Abu-CONH-ethyl) 

A cell-permeable, potent, reversible, active site inhibitor of calpain I 

and calpain II (K ~250 nM). 

i 

Calpain Inhibitor XI 208743 [Z-L-Abu-CONH(CH ) -morpholine] 

2 3 

A cell-permeable, potent, highly selective, reversible, active site 

inhibitor of calpain I (K = 40 nM) and calpain II (K = 4 nM). 

i i 

Calpain Inhibitor XII 208744 (Z-L-Nva-CONH-CH -2-Py) 

2 

A cell-permeable, potent, highly selective, reversible, active site 

inhibitor of calpain I (K = 9 nM) and calpain II (K = 20 nM). 

i i 

Calpastatin, Human, 

Recombinant, Domain I 

208900 An endogenous protease inhibitor that acts specifically on calpain 

I. Has greater inhibitory action compared to ALLM and ALLN. Not 

available for sale in Japan. 

Calpastatin Peptide 208902 (CS Peptide) 

A cell-permeable and potent inhibitor of calpain I and calpain II 

(IC = 20 nM for purified rabbit calpain II). 

50 

Calpastatin Peptide, Negative 

Control 

References: 

Bartoli, M., and Richard, I. 2005. Int. J. Biochem. Cell Biol. 37, 2 5. 

Tompa, P., et al. 2004. J. Biol. Chem. 279, 20775. 

Goll, D.E., et al. 2003. Physiol. Rev. 83, 73 

Nakajima, T., et al. 200 . Biochim. Biophys. Acta 1519, 55. 

Kinbara, K., et al. 998. Biochem. Pharmacol. 56, 4 5. 

Kampfl, A., et al. 997. J. Neurotrauma 14, 2 . 

Kinbara, K., et al. 997. Arch. Biochem. Biophys. 342, 99. 

Johnson, G.V.W., and Guttmann, R.P. 997. BioEssays 19, 0 . 

Sorimachi, H., et al., 997. Biochem. J. 328, 72 . 

Bartus, R.T., et al. 995. Neurol. Res. 17, 249. 

Saito, K., et al. 993. Proc. Natl. Acad. Sci. USA 90, 2628. 

More online... www.calbiochem.com/inhibitors/calpain 

208904 A scrambled peptide with an identical amino acid composition to that 

of Calpastatin Peptide (Cat. No. 208902). Useful as a negative control 

for Calpastatin Peptide. 

Calpastatin, Human Erythrocytes 208901 Tetrameric protein that is a specific, endogenous inhibitor of the 

calcium-activated neutral proteinases. It is upregulated in response to 

hypoxia and may have a protective role in minimizing hypoxic damage. 

Calpeptin 03-34-0051 (Benzyloxycarbonylleucyl-norleucinal) 

A cell-permeable calpain inhibitor. Inactivates calpain I (ID 50 = 52 nM), 

calpain II (ID 50 = 34 nM), and papain (ID 50 = 38 nM). 

25 mg $ 70 

5 mg 

25 mg 

$48 

$ 72 

5 mg $63 

25 mg $ 9 

mg $ 90 

mg $ 90 

mg 

5 mg 

mg 

5 mg 

mg 

5 mg 

mg 

5 mg 

mg 

3 mg 

$50 

$ 79 

$84 

$288 

$84 

$288 

$84 

$288 

$ 78 

$446 

500 mg $ 44 

500 mg $ 30 

00 mg $ 92 

5 mg 

25 mg 

00 mg 

$70 

$ 97 

$573 


Phone 800 628 8470 


5

Proteases 

Calpain Inhibitors, continued 


EST 330005 [E-64d; (2S,3S)-trans-Epoxysuccinyl-L-leucylamido-3-methylbutane Ethyl 

Ester; Loxistatin] 

A cell-permeable, irreversible inhibitor of cysteine proteases that is 

reported to block the action of calpain I. Its action is similar to E-64 

(Cat. No. 324890); however, it is devoid of charged groups. 

mg $96 

PD 45305 513021 A useful negative control for the calpain inhibitors PD 50606 

(Cat. No. 5 3022) and PD 5 746 (Cat. No. 5 3024). 

mg $99 

5 mg $94 

PD 50606 513022 [3-(4-Iodophenyl)-2-mercapto-(Z)-2-propenoic Acid] 

A cell-permeable, selective non-peptide calpain inhibitor (K i = 2 0 nM 

for calpain I and 370 nM for calpain II) directed towards the calcium 

binding sites of calpain. 

PD 5 746 513024 [3-(5-Fluoro-3-indolyl)-2-mercapto-(Z)-2-propenoic Acid] 

A cell-permeable, non-peptidic, and highly selective calpain inhibitor 

that displays over 20-fold greater selectivity for calpain I (K = 260 nM) 

i 

over calpain II (K = 5.33 mM). 

i 

Calpain Inhibitor Set 208733 Provided as a 5 vial set. Each set contains 5 mg ALLN (Cat. No. 2087 9); 

25 mg Calpain Inhibitor III (Cat. No. 208722); 5 mg of Calpeptin (Cat. 

No. 03-34-005 ); mg of EST (Cat. No. 330005); and 5 mg of PD 

50606 (Cat. No. 5 3022). 


Calpain-1 Substrate II, Fluorogenic 

An internally quenched peptide substrate that is optimized for calpainamino 

acid recognition motifs at the primed as well as the nonprimed 

sides. 

Cat. No. 208772 1 mg $180 

Calpain Substrate III, Fluorogenic 

A fluorogenic FRET peptide with a substrate sequence that is optimized 

for calpain- and -2 (Cat. Nos. 2087 2, 2087 3, 2087 5, and 2087 8) 

based on 06 known cleavage sites. It is cleaved by mammalian 

calpains with a much better efficacy (k cat /K mx 0 -2 M - s - ) = 69.8, 

38.5, 20.0, 6.8 , 3.58, 0.05, and < 0.05 for calpain-2, trypsin, papain, 

calpain-B, calpain-A, chymotrypsin, and cathepsin-B, respectively) 

and kinetically superior to other commonly used calpain substrates, 

such as LY-AMC (Cat. No. 20873 ) and a-spectrin cleavage site-based 

substrate (Cat. No. 208748). Has been used successfully in monitoring 

calpain activity in whole Drosophila S2 cells (cellular incorporation 

achieved with a lipofection reagent) and in COS-7 cell lysate. 

Purity: ≥98% by HPLC. 

Cat. No. 208771 1 mg $195 

Calpain Activity Assay Kit, Fluorogenic 

Assay kit useful for the quantitative determination of calpain- and 

calpain-2 activity in human cell lysates, plasma, and serum and for 

screening calpain inhibitors. Requires a fluorimeter or microplate 

reader capable of measuring fluorescence at wavelengths of 

Ex. max: ~360 nm and Em. max: ~460 nm. 

Cat. No. QIA120 1 kit $345 

Calpain Substrate II, Fluorogenic 

Cyclic fluorogenic substrate for the quantitative determination of 

calpain - and -2. Also suitable for measuring the peptidase activity of 

the 20S proteasome. Typical concentrations range from 0– 00 µM, 

depending on assay conditions. Purity: ≥95% by TLC. Ex. max.: ~380 nm, 

Em. max.: ~460 nm. 

Cat. No. 208731 25 mg $75 

Calpain-1 Substrate, Fluorogenic 

2 mg $ 69 

set $325 

An internally quenched fluorogenic substrate peptide derived from the 

calpain- cleavage site of a-spectrin. It is not recognized by trypsin 

or a-chymotrypsin and serves as a sensitive and specific substrate for 

calpain- (K m = 4.6 µM; k cat = s - ). Cleavage occurs between Tyr-Gly 

residues and results in enhanced fluorescence. Purity: ≥95% by HPLC. 

Ex. max.: ~490 nm, Em. max.: ~518 nm. 

Cat. No. 208748 2 mg $163 

View more than 20 anti-calpain 

antibodies at our updated 

Antibody Resource 

www.calbiochem.com/ 

antibodyresource 

6 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Collagenase Inhibitors 

(Also see Matrix Metalloproteinase Inhibitors) 

Mammalian collagenases belong to the family of 

metalloproteinases that specifically cleave collagen. 

On a dry weight basis, collagen constitutes over 70% 

of skin weight. Collagenases have a unique ability to 

degrade native collagen that is normally resistant to 

breakdown by other proteases. They catalyze a single 

proteolytic cleavage in the helical collagen chains, 

resulting in two fragments that are subsequently 

accessible to less specific proteases. Collagenases are 

produced by macrophages, fibroblasts, and keratinocytes 

that are involved in the wound-healing process. In 

normal healthy subjects, even during wound healing, 

the activity of endogenous collagenases is low and is 

Collagenase Inhibitors 


Proteases 

sufficient for the removal of dead tissue. However, in 

patients with chronic non-healing wounds and ulcers, 

there may be impairment of endogenous collagenase 

production leading to insufficient removal of dead 

tissue. Such conditions warrant the application of 

bacterial collagenases to clean the wound and begin the 

healing process. Collagenases also play an important 

role in separating cells from their anchors. They dissolve 

desmosomes and thereby enable cells to migrate on a 

matrix of fibronectin. Fibroblast migration also requires 

these proteases to enable fibroblasts to move within the 

wound. 


Collagenase Inhibitor I 234140 (Z-PDLDA-NHOH) 

A potent and specific inhibitor of vertebrate collagenases (IC 50 = mM). 

TAPI-0 579050 {N-(R)-[2-(Hydroxyaminocarbonyl)methyl]-4-methylpentanoyl-Lnaphthylalanyl-L-alanine 

Amide; TNF-a Protease Inhibitor-0} 

A hydroxymate-based inhibitor of collagenase, gelatinase, and TACE 

[TNF-a convertase; ADAM 7 (IC 50 = 00 nM)]. 

TAPI- 579051 {N-(R)-[2-(Hydroxyaminocarbonyl)methyl]-4-methylpentanoyl-Lnaphthylalanyl-L-alanine, 

2-aminoethyl Amide; TNF-a Protease Inhibitor-1} 

A structural analog of TAPI-0 (Cat. No. 579050) with similar in vitro 

efficacy for the inhibition of MMPs and TACE. 

5 mg $55 

mg $262 

mg $262 

N InSolution TAPI- 579053 A 0 mM (500 mg/ 00 ml) solution of TAPI- (Cat. No. 57905 ) in DMSO. 500 mg $ 39 


Collagenase Substrate II 

An excellent substrate for a convenient, continuous spectrophotometric 

assay of collagenases. Change in absorption is monitored at ~304 nm. 

Purity: ≥98% by TLC. 

Cat. No. 234147 5 mg $65 

More online... www.calbiochem.com/inhibitors/collagenase 

Collagenase Substrate III, Fluorogenic 

A quenched-fluorescence substrate useful for measuring clostridial 

collagenase and Pz-peptidase (K m = 8.6 mM). It is not subject to 

interference by background fluorescence of tryptophan-containing 

proteins. Purity: ≥95% by HPLC. Ex. max.: ~345 nm, Em. max.: ~405 nm. 

Cat. No. 234164 5 mg $145 


Phone 800 628 8470 


7

Proteases 

Elastase Inhibitors 

Elastases are serine proteases that hydrolyze amides and 

esters. They are distinctive in their action upon elastin. 

Because elastin is found in highest concentrations 

in the elastic fibers of connective tissues, elastase 

is frequently used to dissociate tissues that contain 

extensive intercellular fiber networks. For this purpose 

they are used in association with other enzymes such as 

collagenase, trypsin, and chymotrypsin. 

Elastase Inhibitors 

Elastase is also found in blood components and this 

enzyme is identical to pancreatic elastase, but differs 

from the elastase of polymorphonuclear leukocytes. The 

leukocyte enzyme, which is inhibited by a 1 -antitrypsin 

but not by pancreatic trypsin inhibitor, is known to 

mediate pathological elastolysis during acute arthritis 

and pulmonary emphysema. 


a -Antitrypsin, Human Plasma 178251 (a 1 -AT; 3.5S a 1 -Glycoprotein; a 1 -Proteinase Inhibitor) 

A serine protease inhibitor that also acts as a major physiological 

regulator of elastase. 


A cell-permeable inhibitor of neutrophil elastase (IC 50 = 93 mM). Also 

acts as a selective, non-competitive inhibitor of 5-lipoxygenase 

(ID 50 = 3.7 mM), glutathione S-transferases, and xanthine oxidase. 

Elastase Inhibitor I 324692 (Boc-AAA-NHO-Bz; PPE Inhibitor) 

A serine protease inhibitor that inhibits pancreatic elastase 

(K i = 28 M - sec - ) and thermitase. 

Elastase Inhibitor II 324744 (HNE Inhibitor; MeOSuc-AAPA-CMK; MSACK) 

A potent inhibitor of human neutrophil elastase (HNE) . The inhibition 

results from cross-linking of catalytic residues at His 57 and Ser 95 . 

Elastase Inhibitor III 324745 (HLE Inhibitor; MeOSuc-AAPV-CMK) 

A potent inhibitor of human leukocyte elastase (HLE) (K i = 0 mM). 

N Elastase Inhibitor IV 324759 [N-(2-(4-(2,2-Dimethylpropionyloxy)phenylsulfonylamino)benzoyl)aminoac 

etic acid; N-(o-(p-Pivaloyloxybenzene)sulfonylaminobenzoyl)glycine] 

Furin Inhibitors 

Furin Inhibitors 

More online... www.calbiochem.com/inhibitors/elastase 

A cell-permeable, potent, substrate-competitive, and highly specific 

inhibitor of neutrophil elastase (IC 50 = 9-49 nM. Displays > 00fold 

greater selectivity over pancreas elastase (IC 50 = 5.6 mM). Does 

not inhibit trypsin, thrombin, plasmin, kallikrein, chymotrypsin, and 

cathepsin G even at concentrations as high as 00 mM. 

8 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

$74 

$287 

500 mg $48 

mg $92 

5 mg $98 

5 mg $ 04 

mg $68 


Furin Inhibitor I 344930 (Decanoyl-RVKR-CMK) 

A peptidyl chloromethylketone that binds to the catalytic site of furin 

and blocks its activity. Hence, it can be used as a high specificity 

cleavage inhibitor of viral glycoproteins and blocker of viral replication. 

Reported to block the shedding of MT5-MMP by furin and prevent 

the activation of MT5-MMP. Also shown to reduce the pro-peptide 

cleavage of BACE (b-site APP-cleaving enzyme). 

mg $ 06 

Furin Inhibitor II 344931 [Hexa-D-arginine; H-(D)RRRRRR-NH ] 2 

A polyarginine compound that acts as a potent, specific, and competitive 

inhibitor of furin (K = 06 nM). Inhibits subtilisin-like proprotein 

i 

convertase 4 (PACE4) and prohormone convertase (PC ) at much higher 

concentration (K = 580 nM and 3 mM, respectively). Has a stimulatory 

i 

effect on the activity of prohormone convertase 2 (PC2). The D-peptides 

are suggested to be more resistant to in vivo hydrolysis than L-peptides. 

mg $87

Matrix Metalloproteinase (MMP) Inhibitors 

The proteolytic degradation of the extracellular matrix 

(ECM) by tumor cells requires the action of highly 

specialized MMPs that are expressed in cell- or tissuespecific 

patterns. MMPs also play an important role 

in wound healing, angiogenesis, embryogenesis, and 

in pathological processes such as tumor invasion and 

metastasis. MMPs are characterized by the presence 

of a zinc ion in the active site, which is required for 

their catalytic activity. Thus far 28 different types 

of MMPs (secreted or transmembrane enzymes) have 

been identified and classified based on their protein 

domain structures derived from genomic data. Of these, 

23 MMPs have been found to be expressed in human 

tissues. Secreted MMPs include minimal-domain MMPs, 

simple hemopexin domain-containing MMPs, gelatinbinding 

MMPs, furin-activated MMPs, and vitronectinlike 

insert MMPs. The membrane-bound MMPs include 

type I transmembrane MMPs, glycosyl-phosphatidyl 

inosital (GPI)-linked MMPs, and type II transmembrane 

MMPs. (Please see table on the next page). 

All MMPs sequenced to date have at least three domains 

in common. The prodomain contains a highly conserved 

segment of eight amino acids that folds over to cover 

the catalytic site and helps to maintain the inactive 

conformation following the release of MMPs. Cleavage 

of the prodomain destabilizes the inhibitory interaction 

between the unpaired cysteine in the sequence and 

the active site zinc. The catalytic domain contains the 

conserved structural metal-binding sites consisting 

of 106 to 119 residues. MMPs also contain a highly 

conserved zinc-binding active site domain containing 

52 to 58 amino acids. The zinc-binding domain contains 

three His residues that occupy three of the coordination 

sites of the active site Zn 2+ . In addition to these, the 

hemopexin-like domain found in all MMPs (except 

MMP-7) plays a role in substrate specificity. 

The activation of MMPs is dependent mainly on 

urokinase-type (uPA) and tissue-type (tPA) plasminogen 

activators that cleave plasminogen into active plasmin. 

A major control point in the regulation of active enzyme 

is inhibition of the active form by the TIMP family of 

inhibitors (21-28 kDa). TIMPs regulate the function of 

MMPs either by inhibiting active MMPs or by controlling 

their activation process. They form tight, non-covalent 

inhibitory complexes with MMPs (K d = 10–50 pM). 


Collagenase 

Family 

MMP-1, 8, 

13, 18 

Gelatinase 

Family 

MMP-2, 9 

Stromelysin Family 

MMP-3, 10, 11 

Membrane-Type 

Family 

MMP-14, 15, 

16, 17 

Matrilysin 

MMP-7 

Proteases 

MMPs facilitate tumor cell invasion and metastasis by at 

least three distinct mechanisms: (a) by eradicating physical 

barriers to invasion through degradation of collagens, 

laminins, and proteoglycans in the ECM, (b) by modulating 

cell adhesion and enabling cells to form new cell-to-cell 

and cell-to-matrix attachments while breaking the existing 

ones, and (c) by acting on ECM components and other 

proteins to expose hidden biological activities, such as 

release of angiostatin from plasminogen. In normal adults, 

MMP expression is very low except in rapidly remodeling 

tissue, such as wound healing and menstrual endometrium. 

Many control elements, such as secretion of MMPs in their 

latent form and the presence of TIMPs, tend to keep MMPs 

inactive in the ECM. 

References: 

Signal/Prodomain Catalytic Domain Hinge Hemopexin 

PRCGVPD 

Region 

RXKR 

Gelatin Binding 

Gueders, M.M. etal. 2006. Eur. J. Pharmacol. 533, 33. 

Elkington, P.T. etal. 2005. Clin. Exp. Immunol. 142, 2. 

Bode, W. 2003. Biochem. Soc. Symp. 70, . 

Fingleton, B. and Matrisian, L.M. 200 . Curr. Opin. Oncol. 13, 368. 

More online... www.calbiochem.com/inhibitors/MMP 

Transmembrane 


Phone 800 628 8470 


9

Proteases 

Matrix Metalloproteinase (MMP Groups) 

Group MMP 

Simple Hemopexin Domain-Containing MMPs MMP- , MMP-3, MMP-8, MMP- 0, MMP- 2, MMP- 3, 

MMP- 8, MMP- 9, MMP-20, MMP-22, and MMP-27 

Gelatin-Binding MMPs MMP-2 and MMP-9 

Furin-Activated Secreted MMPs MMP- and MMP-28 

Vitronectin-Like Insert MMPs MMP-2 

Minimal Domain MMPs MMP-7 and MMP-26 

GPI-linked MMPs MMP- 7 and MMP-25 

Type I Transmembrane MMPs MMP- 4, MMP- 5, MMP- 6, and MMP-24 

Type II Transmembrane MMPs MMP-23 

Matrix Metalloproteinase Inhibitors 


Chlorhexidine, Dihydrochloride 220557 1,6-bis[N´-(p-Chlorophenyl)-N5-biguanido]hexane, 2HCl, CH 

An antimicrobial agent that acts as an inhibitor of MMP-2 and MMP-9; 

however, MMP-2 is more sensitive to chlorhexidine than MMP-9. 

CL-82 98 233105 A selective inhibitor of MMP- 3 (IC = 0 mM) that does not appear 

50 

to act by chelating Zn2+ . Binds within the entire S ´ pocket of MMP- 3, 

docking with the morpholine ring adjacent to the catalytic zinc atom. 

Does not inhibit MMP- , MMP-9, or TACE. 

GM 489 364200 {N-[(2R)-2-(Carboxymethyl)-4-methylpentanoyl]-L-tryptophan-(S)methyl-benzylamide} 

A potent broad-spectrum inhibitor of MMPs. Inhibits MMPs in vitro 

(K = 200 pM for MMP- ; 500 nM for MMP-2; 20 mM for MMP-3; 

i 

00 nM for MMP-8; 00 nM for MMP-9). 

GM 600 364205 {Galardin; N-[(2R)-2-(Hydroxamidocarbonylmethyl)-4-methylpentanoyl]- 

L-tryptophan Methylamide} 

A potent broad-spectrum hydroxamic acid inhibitor of MMPs. Inhibits 

MMPs in vitro (K = 400 pM for skin fibroblast MMP- ; 500 pM for 

i 

MMP-2; 27 nM for MMP-3; 0. nM for MMP-8; and 200 pM for MMP-9). 

00 mg $28 

5 mg $96 

N InSolution GM600 364206 A 0 mM ( mg/257 ml) solution of GM600 (Cat. No. 364205) in DMSO. mg $62 

GM 600 , Negative Control 364210 (N-t-Butoxycarbonyl-L-leucyl-L-tryptophan Methylamide) 

A useful negative control for the MMP inhibitor GM 600 

(Cat. No. 364205). 

MMP Inhibitor I 444250 (FN-439) 

An inhibitor of MMP- and MMP-8 (IC = .0 mM), MMP-9 

50 

(IC = 30 mM), and MMP-3 (IC = 50 mM). 

50 50 

MMP Inhibitor II 444247 {N-Hydroxy-1,3-di-(4-methoxybenzenesulphonyl)-5,5-dimethyl-[1,3]piperazine-2-carboxamide} 

An inhibitor of MMP- (IC = 24 nM), MMP-3 (IC = 8.4 nM), MMP-7 

50 50 

(IC = 30 nM), and MMP-9 (IC = 2.7 nM). 

50 50 

MMP Inhibitor III 444264 A homophenylalanine-hydroxamic acid based broad-spectrum cellpermeable, 

reversible inhibitor of matrix metalloproteinases (supplied 

as a racemic mixture). Inhibits MMP- (IC = 7.4 nM), MMP-2 

50 

(IC = 2.3 nM), MMP-3 (IC = 35 nM), MMP-7 (IC = 0– 00 nM), 

50 50 50 

and MMP- 3 (IC = – 0 nM). 

50 

MMP Inhibitor IV 444271 (HONH-COCH CH CO-FA-NH ) 

2 2 2 

A peptide hydroxamic acid that inhibits MMPs and pseudolysin from 

P. aeruginosa (~500 nM). 

MMP-2 Inhibitor I 444244 (OA-Hy; cis-9-Octadecenoyl-N-hydroxylamide; Oleoyl-N-hydroxylamide) 

A potent inhibitor of MMP-2 (K i = .7 mM). 

MMP-2 Inhibitor II 444286 An oxirane analog of SB-3CT, pMS (Cat. No. 444285) that acts as a 

selective, active site-binding, irreversible inhibitor of MMP-2 

(K i = 2.4 µM). 

20 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

5 mg 

mg 

5 mg 

mg 

5 mg 

$62 

$20 

$62 

$20 

$62 

$20 

0 mg $ 36 

mg $ 5 

mg $ 0 

5 mg $ 0 

0 mg $67 

5 mg $ 44

Matrix Metalloproteinase Inhibitors, continued 


Proteases 


MMP-2/MMP-3 Inhibitor I 444239 {N-[[(4,5-Dihydro-5-thioxo-1,3,4-thiadiazol-2-yl)amino]carbonyl]-Lphenylalanine 

Methyl Ester} 

A potent inhibitor of MMP-2 (K i = 7 mM) and MMP-3 (K i = 290 nM). 

MMP-2/MMP-3 Inhibitor II 444240 {a-[[[4,5-Dihydro-5-thioxo-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino]- 

((2-pyridyl)piperazinyl)-(S)-benzenepropanamide} 

A potent inhibitor of MMP-2 (K i = 4.5 mM) and MMP-3 (K i = 520 nM). 

MMP-2/MMP-9 Inhibitor I 444241 {(2R)-2-[(4-Biphenylylsulfonyl)amino]-3-phenylpropionic Acid} 

A potent inhibitor of MMP-2 (IC 50 = 3 0 nM) and MMP-9 (IC 50 = 240 nM). 

MMP-2/MMP-9 Inhibitor II 444249 {(2R)-[(4-Biphenylylsulfonyl)amino]-N-hydroxy-3-phenylpropionamide} 

A potent inhibitor of type IV collagenases, MMP-2 (IC 50 = 7 nM) and 

MMP-9 (IC 50 = 30 nM). 

MMP-2/MMP-9 Inhibitor III 444251 A cyclic peptide that acts as a potent inhibitor of MMP-2 (IC 50 = 0 mM) 

and MMP-9 (IC 50 = 0 mM). 

MMP-2/MMP-9 Inhibitor IV 444274 (SB-3CT) 

A potent, selective, slow-binding, and mechanism-based inhibitor of 

human MMP-2 (K i = 3.9 nM) and MMP-9 (K i = 600 nM). Does not 

affect the activities of MMP- (K i = 206 mM) MMP-3 (K i = 5 mM), or 

MMP-7 (K i = 96 mM). 

N MMP-2/MMP-9 Inhibitor V 444285 A cell-permeable sulfonamido analog of SB-3CT (Cat. No. 444274) that 

displays enhanced aqueous solubility and improved selectivity 

(K i = 6 nM, 80 nM, and 900 nM for MMP-2, -9 and - 4, respectively). 

Binds to the active-site and acts as a mechanism-based, irreversible 

inhibitor of MMPs. 

MMP-3 Inhibitor I 444218 (Ac-RCGVPD-NH 2 ; Stromelysin-1 Inhibitor) 

An inhibitor of MMP-3 (IC 50 = 5 mM). Based on a segment from the 

conserved region of the N-terminal propeptide domain. 

MMP-3 Inhibitor II 444225 [N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic Acid; NNGH] 

A potent inhibitor of human MMP-3 (K i = 30 nM). 

MMP-3 Inhibitor III 444242 {N-[[(4,5-Dihydro-5-thioxo-1,3,4-thiadiazol-2-yl)amino]carbonyl]-Lphenylalanine} 

A potent inhibitor of MMP-3 (K i = 3.2 mM) that inhibits MMP-2 only at 

higher concentrations (K i >200 mM). 

MMP-3 Inhibitor IV 444243 {a-[[[(4,5-Dihydro-5-thioxo-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino] 

-N-(cyclohexylmethyl)-(S)-benzenepropanamide} 

A potent inhibitor of MMP-3 (K i = 8 0 nM) that inhibits MMP-2 only at 

higher concentrations (K i >200 mM). 

MMP-3 Inhibitor V 444260 (4-Dibenzofuran-2´-yl-4-hydroximino-butyric Acid) 

A potent and competitive inhibitor of MMP-3. Inhibits both human and 

rabbit MMP-3 (wild type and mutants) with K i values in the low mM range. 

MMP-3 Inhibitor VI 444265 [4-(4´-Biphenyl)-4-hydroxyimino-butyric Acid] 

A potent and competitive inhibitor of MMP-3. Inhibits both human and 

rabbit MMP-3 (wild type and mutants) with K i values in the low mM range. 

MMP-3 Inhibitor VII 444280 {3-[4-(4-cyanophenyl)phenoxy]propanohydroxamic Acid} 

A potent nonpeptide inhibitor of MMP-3 (stromelysin; IC 50 = 25 nM 

against the catalytic domain). 

MMP-3 Inhibitor VIII 444281 {N-Hydroxy-2(R)-{[(4-methoxyphenyl)sulfonyl]-[benzylamino]}-4methylpentanamide} 

A cell-permeable, potent inhibitor of human MMP-3 (stromelysin; 

K i = 23 nM) and murine macrophage metalloelastase (MME/MMP- 2; 

IC 50 = 3 nM). 

MMP-8 Inhibitor I 444237 {(3R)-(+)-[2-(4-Methoxybenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline- 

3-hydroxamate]} 

MMP-8 Inhibitor I, 


A potent inhibitor of MMP-8 (IC 50 = 4 nM). 

444238 {(3S)-(–)-[2-(4-Methoxybenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline- 

3-hydroxamate]} 

A negative control for MMP-8 Inhibitor I (Cat. No. 444237; IC 50 = mM). 

5 mg $ 46 

2 mg $ 5 

5 mg $ 46 

mg $ 5 

mg $ 36 

500 mg $ 23 

500 mg $ 34 

5 mg $202 

5 mg $85 

2 mg $ 42 

2 mg $ 7 

5 mg $84 

5 mg $55 

mg $ 03 

5 mg $ 78 

mg $79 

mg $55 


Phone 800 628 8470 


2

Proteases 

Matrix Metalloproteinase Inhibitors, continued 


MMP-9 Inhibitor I 444278 A potent and selective inhibitor of MMP-9 (IC 50 = 5 nM). Inhibits 

MMP- (IC 50 = .05 mM) and MMP- 3 (IC 50 = 3 nM) only at much 

higher concentrations 

MMP-9/MMP- 3 Inhibitor I 444252 [N-Hydroxy-1-(4-methoxyphenyl)sulfonyl-4-(4-biphenylcarbonyl)piperaz 

ine-2-carboxamide] 

A highly-potent, piperazine-based inhibitor of MMP-9 and MMP- 3 

(IC 50 = 900 pM). Inhibits MMP- and MMP-3 at much higher 

concentrations (IC 50 = 43 nM and 23 nM, respectively). Also acts as 

an inhibitor of MMP-7 (IC 50 = 930 nM). 

MMP-9/MMP- 3 Inhibitor II 444253 [N-Hydroxy-1-(4-methoxyphenyl)sulfonyl-4-benzyloxycarbonylpiperazine- 

2-carboxamide] 

A highly-potent, piperazine-based potent inhibitor of MMP-9 (IC 50 = 

.9 nM) and MMP- 3 (IC 50 = .3 nM). Inhibits MMP- and MMP-3 at 

higher concentrations (IC 50 = 24 nM and 8 nM, respectively). Also acts 

as a weak inhibitor of MMP-7 (IC 50 = 230 nM). 

N MMP- 3 Inhibitor 444283 [Pyrimidine-4,6-dicarboxylic acid, bis-(4-fluoro-3-methyl-benzylamide)] 

A pyrimidine dicarboxamide compound that potently inhibits MMP- 3 

activity (IC 50 = 8 nM) with expected selectivity over MMP- , -2, -3, -7, 

-8, -9, - 0, - 2, - 4, and - 6 as determined by conformational structure 

analysis. Shown to bind to the MMP- 3 catalytic domain and act as a 

non-zinc-chelating inhibitor. 

DL-Thiorphan 598510 {N-[(RS)-2-Benzyl-3-mercaptopropanoyl]-glycine} 

A thiol containing amido-acid that selectively binds to the active site 

zinc of metalloproteinases and blocks their activity (IC 50 = 2. nM for 

neutral endopeptidase-NEP). Although it is shown to inhibit the activity 

for Ab peptide degrading enzyme neprilysin in vitro, it has no effect on 

the secretion of Ab peptide or amyloid b precursor protein (APP). Also 

inhibits the activity of angiotensin-converting enzyme (ACE) at much 

higher concentrations (IC 50 = 4 mM); however, it does not affect the 

activity of endothelin-converting enzyme. 

XG076 682300 7-Aza-2-phenylbenzisothizol-3-one 

An isothiazolone derivative that inhibits the activation of pro-MMPs 

but does not affect the activity of active MMPs. 


MMP-1 ELISA Kit 

The MMP- ELISA is a non-isotopic colorimetric assay kit for the in 

vitro quantification of human MMP- protein in tissue culture medium 

and serum. Not available for sale in Japan. 



A non-isotopic colorimetric assay for the in vitro assay of human 

MMP-2 protein in tissue culture media, serum, or plasma. Not available 




A sandwich ELISA based kit designed specifically for assay of MMP-9 in 

human cell lines in suspension or adherent cells. Not available for sale 

in Japan. 



500 mg $96 

mg $87 

mg $ 02 

mg $93 

0 mg $ 95 

5 mg $ 27 

A sandwich ELISA based kit that can be used to assay of MMP-3 in cells 

in suspension and in adherent cells. Not available for sale in Japan. 



A highly sensitive and specific kit for detection of active MMP- 3 

from human samples, including serum, synovial fluid, and cell culture 

supernatant. Does not recognize MMP- , MMP-2, MMP-3, MMP-8, 

MMP-9, or the latent form of MMP- 3. 


InnoZyme Gelatinase Activity Assay Kit, Fluorogenic 

A sensitive fluorogenic assay (Ex. max: ~325 nm; Em. max.: ~393 nm) 

for the measurement of gelatinases (MMP-2 and MMP-9). Also useful 

for the screening of gelatinase inhibitors. 

Cat. No. CBA003 1 kit $375 

22 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) 

Tissue inhibitors of metalloproteinases (TIMPs) are a 

family of ubiquitous, endogenous inhibitors that regulate 

the activation and activity of matrix metalloproteinases 

(MMPs). They have been shown in animal models to 

be capable of the inhibition of tumor cell invasion and 

metastasis. They may also be involved in other diseases 

such as arthritis and periodontal disease. TIMP-1 is 

a 184 amino acid glycoprotein of 28.5 kDa. TIMP-1 

preferentially binds and inhibits MMP-9 and MMP- 

1 through interaction with their catalytic domains. 

TIMP-2 is a 194 amino acid, non-glycosylated protein 

of 21 kDa with 43% and 44% homology to TIMP-1 and 

TIMP-3, respectively. It inhibits the activity of all active 

MMPs and regulates MMP-2 expression by binding to 

the C-terminal region of pro-MMP-2 (K d ~5 nM). As 

with TIMP-1, TIMP-2 has been shown to have erythroidpotentiating 

activity and cell growth-promoting 

Tissue Inhibitors of Matrix Metalloproteinases 


Proteases 

activity. TIMP-3 is present in the eye. It is tightly bound 

to the extracellular matrix and has been shown to 

inhibit TNF-a converting enzyme (TACE). A mutation 

in TIMP-3 is found in Sorsby's fundus dystrophy, a 

dominantly-inherited form of blindness. TIMP-4 blocks 

the activities of several (MMPs) implicated in the 

arthritic cartilage erosion. 

References: 

Visse, R., and Nagase, H. 2003. Cir. Res. 92, 827. 

Cheung, P.Y., et al. 200 . Proc. West Pharmacol. Soc. 44, 97. 

Mannello, F., and Gazzanelli, G. 200 . Apoptosis 6, 479. 

Herbst, H., et al. 997. Am. J. Pathol. 150, 647. 

Jung, K., et al. 997. Int. J. Cancer 74, 220. 

Rivera, S., et al. 997. J. Neurosci. 17, 4223. 

Vallon, R., et al. 997. Eur. J. Biochem. 244, 8 . 

Cottam, D.W., et al. 993. Intl. J. Oncol. 2, 86 . 

Stetler-Stevenson, W.G. et al. 993. FASEB J. 7, 434. 


TIMP- , Recombinant, Bovine PF020 (Tissue Inhibitor of Metalloproteinase-1) 

A CHO cell-derived protein. Shown to inhibit MMP- (IC 50 = –5 nM). 


TIMP- , Human Neutrophil 

Granulocyte 

612080 (Tissue Inhibitor of Metalloproteinase-1) 

A 28 kDa glycoprotein that forms a non-covalent stochiometric 

complex with latent and active MMPs. Binds to pro-MMP-9 and 

MMP-9 via their C-terminal domains. 

TIMP- , Recombinant, Human PF019 (Tissue Inhibitor of Metalloproteinase-1) 

A 28 kDa glycoprotein that is expressed by a variety of cell types. It 

forms a non-covalent, stoichiometric complex with both latent and 

active MMPs. TIMP- preferentially binds and inhibits MMP-9. Not 

available for sale in Japan. 

TIMP-2, Human Rheumatoid 

Synovial Fibroblast 

More online... www.calbiochem.com/inhibitors/TIMPs 

612084 (Tissue Inhibitor of Metalloproteinase-2) 

Forms a non-covalent stoichiometric complex with latent and active 

MMPs. Shown to inhibit the activities of MMP- , MMP-2, MMP- 2, and 

transin. 

TIMP-2, Human, Recombinant PF021 (Tissue Inhibitor of Metalloproteinase 2) 

A 2 kDa (nonreduced) or a 24 kDa (reduced) protein expressed by a 

variety of cell types. Forms a non-covalent, stoichiometric complex 

with both latent and active MMPs. TIMP-2 preferentially binds and 

inhibits MMP-2. Not available for sale in Japan. 

TIMP-2, Mouse, Recombinant PF098 (Tissue Inhibitor of Metalloproteinase-2) 

A 94 amino acid non-glycosylated protein with 43% and 44% 

homology to TIMP- and TIMP-3, respectively. Inhibits the activity of 

all MMPs and regulates MMP-2 expression by binding to the C-terminal 

region of pro-MMP-2. TIMP-2 is constitutively produced by most cell 

types in culture, along with MMP-2. 

TIMP-3, Human, Recombinant PF095 (Tissue Inhibitor of metalloproteinase-3) 

Constitutively produced by many cell types. Differs from the other 

TIMPs in its localization to the extracellular matrix. TIMP-3 is more 

basic than the other TIMPs, and the basic residues are thought to help 

anchor TIMP-3 into the ECM. 

3 mg $ 53 

5 mg $225 

3 mg $ 53 

5 mg $225 

3 mg $ 53 

5 mg $276 

5 mg $276 


Phone 800 628 8470 


23

Proteases 

Tissue Inhibitors of Matrix Metalloproteinases, continued 


5 mg $276 

TIMP-3, Mouse Recombinant PF096 (Tissue Inhibitor of metalloproteinase-3) 

Constitutively produced by many cell types in culture. Differs from the 

other TIMPs in its localization to the extracellular matrix. Has a more 

basic K i than the other TIMPs, and the basic residues are thought to 

help anchor TIMP-3 into the ECM. TIMP-3 is an efficient ”sheddase“ 

inhibitor, inhibiting ADAM- 7 (TACE) at the low nanomolar levels. 

TIMP-4, Human Fibroblast PF097 (Tissue Inhibitor of metalloproteinase-4) 

Binds to Gelatinase A in manner similar to TIMP-2. Overexpression of 

TIMP-4 is reported to reduce cell invasiveness in vitro. 


TIMP-1 ELISA Kit 

A non-isotopic, colorimetric, sandwich ELISA based kit specific for 

human TIMP- protein in tissue culture media or serum. Not available 



TIMP-2 ELISA Kit 

To view more than 80 MMP/ TIMP-related antibodies, 

visit our Antibody Resource at 

www.calbiochem.com/antibodyresource 

5 mg $276 

A non-isotopic, colorimetric, sandwich ELISA based kit specific for 

human TIMP-2 protein in tissue culture medium, serum, plasma and 

tissue lysates. Not available for sale in Japan. 


24 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Protease Inhibitors 

The proper functioning of the cell requires an optimum 

level of important structural proteins, enzymes, 

and regulatory proteins. One mechanism whereby 

cells achieve this steady state level is by proteolytic 

degradation. Protein degradation exhibits first order 

kinetics and is an energy-dependent, irreversible process 

brought about by the action of several peptidases. 

Peptidases (proteases) can be subdivided into two major 

groups: the endopeptidases and the exopeptidases, which 

cleave peptide bonds either at points within the protein 

or remove amino acids sequentially from either the N- 

or C-terminus, respectively. The term proteinase is also 

used as a synonym for endopeptidase. The International 

Union of Biochemistry and Molecular Biology (IUBMB) 

has recognized four classes of proteases: serine 

proteinases, cysteine proteinases, aspartic proteinases, 

and metalloproteinases. 

In vivo, proteins are either protected in specialized 

compartments or they reside in a special protective 

conformation. Every protein isolated from cells is a 

potential substrate for proteolytic enzymes. Protease 

Protease Inhibitors 


Proteases 

inhibitors are often used in experimental protocols that 

require extraction and analysis of intact proteins. These 

inhibitors block the activity of proteases and minimize 

tissue damage during purification procedures and organ 

perfusion studies. More recently, selected protease 

inhibitors have been used as anti-HIV agents. 

Commonly used protease inhibitors are either synthetic 

or of bacterial or fungal origin. They inhibit protease 

activity in either a reversible or irreversible manner. 

Over 100 naturally occurring protease inhibitors 

have been identified so far. They behave as tightbinding 

reversible or pseudo-irreversible protease 

inhibitors preventing substrate access to the active 

site through steric hindrance. Some of them act by 

modifying an amino acid residue of the protease active 

site. For example, serine proteases are inactivated 

by phenylmethane sulfonyl fluoride (PMSF), which 

reacts with the active site serine, whereas the 

chloromethylketone derivatives react with the histidine 

of the catalytic triad. 

More online... www.calbiochem.com/inhibitors/protease 


mg $ 56 

Acetyl-Pepstatin 110175 [Ac-Val-Val-(3S,4S)-Sta-Ala-(3S,4S)-Sta-OH] 

An aspartyl protease inhibitor that acts as an effective inhibitor of HIVproteinase 

(K i = 20 nM at pH 4.7). 

AEBSF, Hydrochloride 101500 [4-(2-Aminoethyl)benzenesulfonylfluoride, HCl] 

Water-soluble, non-toxic alternative to PMSF. Irreversible inhibitor of 

serine proteases. Reacts covalently with a component of the active 

site. Inhibits chymotrypsin, kallikrein, plasmin, trypsin, and related 

thrombolytic enzymes. 

AEBSF, Immobilized 101501 An immobilized form of the protease inhibitor AEBSF (Cat. No. 0 500) 

covalently attached to hydrophobic acrylic beads. Useful as a scavenger 

for serine proteases where the interfering protease-inhibitor complex 

can be easily removed. 

ALLN 208719 (Calpain Inhibitor I; LLNL; MG 101) 

Inhibits chymotrypsin-like activity of the proteasome (K = 5.7 mM). 

i 

Also inhibits calpain I, calpain II, cathepsin B, and cathepsin L. 

InSolution ALLN 208750 (Calpain Inhibitor I; LLNL; MG 101) 

A 0 mM (5 mg/ .30 ml) solution of ALLN (Cat. No. 2087 9). 

ALLM 208721 (Calpain Inhibitor II) 

Inhibitor of calpain I (K i = 20 nM), calpain II (K i = 230 nM), cathepsin B 

(K i = 00 nM), and cathepsin L (K i = 600 pM). 

Amastatin, Streptomyces sp. 129875 [(2S,3R)-3-Amino-2-hydroxy-5-methylhexanoyl-Val-Val-Asp-OH] 

Binds to cell surfaces and reversibly inhibits aminopeptidases. A 

slow binding, competitive inhibitor of aminopeptidase M and leucine 

aminopeptidase. Has no significant effect on aminopeptidase B. 

e-Amino-n-caproic Acid 1381 (EACA) 

A lysine analog that inhibits carboxypeptidase B. Promotes rapid 

dissociation of plasmin by inhibiting the activation of plasminogen. 

50 mg 

00 mg 

500 mg 

g 

$42 

$69 

$263 

$470 

50 mg $98 

5 mg 

25 mg 

$48 

$ 72 

5 mg $63 

25 mg $ 70 

mg $ 06 

500 g $92 


Phone 800 628 8470 


25

Proteases 

Protease Inhibitors, continued 


N Aminopeptidase N Inhibitor 164602 [APN/CD13 Inhibitor; 2',3-Dinitroflavone-8-acetic acid; 3-Nitro-2-(2nitrophenyl)-4-oxo-4H-1-benzopyran-8-acetic 

acid) ] 

5 mg $95 

a -Antichymotrypsin, Human 

Plasma 

A selective, reversible, and competitive inhibitor of aminopeptidase N 

(APN/CD 3; IC = 25 mM in U937 cells). 

50 

178196 (a -Achy; a -1X-Glycoprotein; a -1X) 

1 1 1 

An acute phase plasma protein that functions as a specific inhibitor of 

chymotrypsin-like serine proteases. 

Antipain, Dihydrochloride 178223 Peptidyl arginine aldehyde protease inhibitor produced by 

actinomycetes. Inhibitor of Ca2+ -dependent endopeptidases. Has 

specificity similar to Leupeptin (Cat. No. 08975). Inhibits trypsin-like 

serine proteases, papain and some cysteine proteases (IC = 300 mM). 

50 

Antipain, Hydrochloride 178220 A reversible inhibitor of cysteine and serine proteases. 5 mg 

0 mg 

a 2 -Antiplasmin, Human Plasma 178221 (Primary Plasmin Inhibitor; a 2 -Protease Inhibitor) 

An inhibitor of plasminogen-activator-induced lysis of fibrin clots. 

Forms a covalent complex with plasmin and inactivates it. 

Antithrombin III, Human Plasma 169756 (ATIII; Factor Xa inhibitor; Heparin cofactor) 

Complexes with serine proteases of blood coagulation system including 

thrombin, plasmin, kallikrein, and factors IXa, Xa, Xla, and XIIa. Potency 

is strongly enhanced in the presence of heparin. 

a -Antitrypsin, Human Plasma 178251 (a -AT; 3.5S a -Glycoprotein; a -Proteinase Inhibitor) 

1 1 1 

A serine protease inhibitor that also acts as a major physiological 

regulator of elastase. 

p-APMSF, Hydrochloride 178281 (p-Amidinophenylmethylsulfonylfluoride, HCl) 

A specific irreversible inhibitor of trypsin-like serine proteases. 

A suitable alternative to DFP and PMSF. 

Aprotinin, Bovine Lung, 

Crystalline 

616370 (Pancreatic Trypsin Inhibitor; Trypsin-Kallikrein Inhibitor) 

A competitive and reversible inhibitor of esterase and protease 

activity. Forms a tight complex with and blocks the active site of 

target enzymes. Inhibits a number of different proteases, including 

chymotrypsin, coagulation factors involved in the pre-phase of blood 

clotting, kallikrein (K d = x 0 -7 M), plasmin (K d = 2.3 x 0 - 0 M), tissue 

and leukocyte proteinases, and trypsin (K d = 5 x 0 - 4 M). 

Aprotinin, Bovine Lung, Solution 616399 (Kallikrein Inactivator) 

A competitive and reversible inhibitor of proteolytic and esterolytic 

activity. A serine protease inhibitor. In cell cultures, extends the life of 

cells and prevents proteolytic damage to intact cells. 

N Aprotinin, Bovine, Recombinant, 

Nicotiana sp., Animal-Free 

616371 A competitive, heat stable, reversible inhibitor of proteolytic and 

esterolytic activity. Effective at concentrations equimolar with 

protease. 

ATBI, Synthetic 189250 (AGKKDDDDPPE; Alkalo-thermophilic Bacillus Inhibitor) 

A potent inhibitor of various aspartyl proteases. Shown to inhibit pepsin 

in a slow-tight binding, competitive manner (K i = 55 pM). Also functions 

as a tight binding, non-competitive inhibitor of HIV- protease that 

functions at the active site of the flap region (K i = 7.8 nM). 

Benzamidine, Hydrochloride 199001 Inhibitor of trypsin and trypsin-like enzymes. Benzamidine derivatives 

have been used in inhibiting the growth of colon carcinoma cells. 

Inhibits factor VII autoactivation. 

Bestatin 200484 {[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanoyl]-Leu} 

Binds to cell surfaces and inhibits cell surface aminopeptidases, notably 

aminopeptidase B and leucine aminopeptidase. Activates macrophages 

and T lymphocytes. Has antitumor properties. 

Bestatin Methyl Ester 200485 {(-)-N-[(2S, 3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine Methyl 

Ester} 

A cell-permeable derivative of Bestatin (Cat. No. 200484) that displays 

slightly stronger inhibition of neutral aminopeptidase than Bestatin but 

has much weaker activity against basic aminopeptidase. 

26 Orders Phone 800 854 34 7 


Fax 800 776 0999 


00 mg 

mg 

$76 

$474 

0 mg $74 

$4 

$76 

00 mg $58 

mg $ 97 

mg 

5 mg 

$74 

$287 

5 mg $90 

0 mg 

20 mg 

00 mg 

00 KU 

500 KU 

mg 

5 mg 

25 mg 

$47 

$79 

$299 

$79 

$29 

$52 

$72 

$ 44 

mg $8 

5 g 

25 g 

$28 

$62 

0 mg $ 0 

5 mg $ 22



Proteases 


CA-074 205530 {Cathepsin B Inhibitor III; [L-3-trans-(Propylcarbamoyl)oxirane-2carbonyl]-L-isoleucyl-L-proline} 

A potent, irreversible inhibitor of Cathepsin B in vivo and in vitro 

(IC 50 = 2.24 nM for rat liver cathepsin B). 

CA-074 Me 205531 {Cathepsin B Inhibitor IV; [L-3-trans-(Propylcarbamoyl)oxirane-2carbonyl]-L-isoleucyl-L-proline 

Methyl Ester} 

Calpastatin, Human, 

Recombinant, Domain I 

A cell-permeable analog of CA-074 (Cat. No. 205530) that acts as an 

inhibitor of intracellular cathepsin B. 

208900 A potent inhibitor of calpain, a Ca 2+ -dependent cysteine protease. Has 

greater inhibitory action than calpain inhibitors I and II. Inhibitory 

sequence has 8 amino acid residues. Not available for sale in Japan. 

Calpeptin 03-34-0051 (Benzyloxycarbonylleucyl-norleucinal) 

A cell-permeable calpain inhibitor. Inactivates calpain I (ID 50 = 52 nM), 

calpain II (ID 50 = 34 nM), and papain (ID 50 = 38 nM). 

Carboxypeptidase Inhibitor, 

Potato 

217359 A potent inhibitor of a wide variety of digestive tract 

carboxypeptidases. In immobilized form, suitable for the purification of 

carboxypeptidases. 

Cathepsin Inhibitor I 219415 (Z-FG-NHO-Bz) 

A selective inhibitor of cathepsin B (k /K = 8.9 x 0 2 i 3 M- sec- ), 

cathepsin L (k /K = 3.8 x 0 2 i 5 M- sec- ), cathepsin S (k /K = 4.2 x 0 2 i 4 M- sec- ), and papain (k /K = .8 x 0 2 i 3 M- sec- ). 

Cathepsin Inhibitor II 219417 (Z-FG-NHO-BzME) 

A selective inhibitor of cathepsin B (k /K = 6.9 x 0 2 i 3 M- sec- ), 

cathepsin L (k /K = 3. x 0 2 i 5 M- sec- ), cathepsin S (k /K = 6.6 x 0 2 i 4 M- sec- ), and papain (k /K = .8 x 0 2 i 3 M- sec- ). 

Cathepsin Inhibitor III 219419 (Z-FG-NHO-BzOME) 

Cysteine protease inhibitor. Selectively inhibits cathepsin B (k /K = 2 i 

.0 x 04 M- sec- ), cathepsin L (k /K = .5 x 0 2 i 5 M- sec- ), cathepsin S 

(k /K = 6.6 x 0 2 i 4 M- sec- ), and papain (k /K = .0 x 0 2 i 3 M- sec- ). 

Cathepsin B Inhibitor I 342000 (Cathepsin B, Inhibitor I; Z-FA-FMK) 

A cathepsin B inhibitor. Also suitable as a negative control for caspase- . 

Cathepsin B Inhibitor II 219385 (Ac-LVK-CHO) 

A more active lysinal analog of leupeptin (Cat. No. 08975). Inhibits 

cathepsin B at nanomolar levels (IC 50 = 4 nM). 

Cathepsin G Inhibitor I 219372 A potent, selective, reversible, and competitive non-peptide inhibitor of 

cathepsin G (IC = 53 nM and K = 63 nM). 

50 i 

Cathepsin K Inhibitor I 219377 [1,3-Bis(N-carbobenzoyloxy-L-leucyl)amino Acetone; 1,3-Bis(CBZ-Leu- 

NH)-2-propanone] 

A cell-permeable, potent, selective, reversible inhibitor of cathepsin K 

(K = 22 nM). Binds to cathepsin K and span both the S- and S´- subsites. 

i 

Cathepsin K Inhibitor II 219379 [1-(N-Benzyloxycarbonyl-leucyl)-5-(N-Boc-phenylalanylleucyl)carbohydrazide; 

Inhibitor Boc-I; Z-L-NHNHCONHNH-LF-Boc] 

A cell-permeable, potent, selective, and reversible inhibitor of cathepsin 

K (K = 6 nM). 

i 

Cathepsin K Inhibitor III 219381 [1-(N-Benzyloxycarbonyl-leucyl)-5-(phenylalanyl-leucyl)carbohydrazide; 

Inhibitor I; Z-L-NHNHCONHNH-LF-NH ] 2 

A cell-permeable, potent, selective, reversible inhibitor of cathepsin K 

(K = 9.7 nM). At higher concentrations also inhibits the activities of 

i,app 

cathepsin L, cathepsin B, and papain (K = 20 nM, 5. mM, and 

i,app 

2.3 mM, respectively). 

Cathepsin L Inhibitor I 219421 (Z-FF-FMK) 

A potent, cell-permeable, and irreversible inhibitor of cathepsins B and L. 

Cathepsin L Inhibitor II 219426 (Z-FY-CHO) 

A potent and selective inhibitor of cathepsin L. 

Cathepsin L Inhibitor III 219427 [Z-FY(t-Bu)-DMK] 

An irreversible cathepsin L inhibitor. About 04-fold more effective 

against cathepsin L (k 2 /K i = 2 x 0 5 M - sec - ) than cathepsin S. 

mg $ 46 

mg $ 46 

mg 

3 mg 

5 mg 

25 mg 

00 mg 

$ 78 

$446 

$70 

$ 97 

$573 

5 mg $77 

mg $ 03 

mg $ 03 

mg $ 03 

mg 

5 mg 

$77 

$3 3 

mg $80 

mg $ 28 

5 mg $ 35 

mg $96 

mg $ 56 

mg $82 

5 mg $62 

5 mg $ 04 


Phone 800 628 8470 


27

Proteases 



Cathepsin L Inhibitor IV 219433 (1-Naphthalenesulfonyl-IW-CHO) 

A potent inhibitor of cathepsin L (IC 50 = .9 nM). Also inhibits the 

release of Ca 2+ and hydroxyproline from bone in an in vitro bone culture 

system. 

Cathepsin L Inhibitor V 219435 [Z-FY(OtBu)-COCHO] 

A slow, tight-binding reversible inhibitor of recombinant human 

cathepsin L (K i = 600 pM). Exhibits over 360-fold greater selectivity for 

cathepsin L compared to cathepsin B (K i = 2 4 nM). 

Cathepsin L Inhibitor VI 219495 [N-(4-Biphenylacetyl)-S-methylcysteine-(D)-Arg-Phe-b-phenethylamide; 

Compound 7] 

An end-protected tripeptide that acts as a highly selective, potent, and 

reversible inhibitor of human recombinant cathepsin-L (K i = 9 nM). 

Cathepsin S Inhibitor 219393 (Z-FL-COCHO) 

A slow, tight-binding reversible inhibitor of recombinant cathepsin S 

(K i = 85 pM). Exhibits over 4 0-fold greater selectivity for cathepsin S 

than for cathepsin B (K i = 76 nM). 

Cathepsin/Subtilisin Inhibitor 219420 (Boc-VF-NHO-Bz-pCl) 

Inhibits members of the cysteine protease family including cathepsin 

L, and members of the serine protease family including subtilisin 

Carlsberg and thermitase. 

Chymostatin 230790 {[(S)-1-Carboxy-2-phenylethyl]-carbamoyl-a-[2-amidohexahydro-4(S)pyrimidyl]-(S)-glycyl-[A 

= Leu; B = Val; or C = Ile]-phenylalaninal} 

A reversible serine and cysteine protease inhibitor. Inhibits 

chymotrypsin-like serine proteases. 

Chymotrypsin Inhibitor I, Potato 230906 A pentamer consisting of 5–8 kDa monomeric subunits. Each 

subunit inhibits one molecule of chymotrypsin. Suppresses radiation 

transformation of C3H/ 0T /2 cells in vitro. 

Cystatin, Egg White 240891 (Ovocystatin) 

A competitive and reversible cysteine protease inhibitor. 

3,4-Dichloroisocoumarin 287815 A potent irreversible inhibitor of serine proteases. Reacts with 

serine proteases to release acyl chloride moiety that can acylate 

another active site residue. Has no action on thiol proteases and 

metalloproteases. 

Diisopropylfluorophosphate 30967 (DFP) 

A potent irreversible inhibitor of serine proteases. Also irreversibly 

inactivates acetylcholinesterase. 

Dipeptidylpeptidase II Inhibitor 317621 (Dab-Pip; L-2,4-Diaminobutyrylpiperidinamide; DPP II Inhibitor) 

A potent and highly specific inhibitor of dipeptidylpeptidase II 

(IC 50 = 30 nM). Displays ~7700-fold greater selectivity for human 

seminal fluid DPP II compared to DPP IV (IC 50 > mM). 

Dipeptidylpeptidase IV Inhibitor I 416200 (Diprotin A) 

A serine protease inhibitor. Inhibits both endo- and exopeptidase 

activities of DPP IV. 

Dipeptidylpeptidase IV Inhibitor II 317638 A reversible inhibitor of dipeptidyl peptidase II (K = 3.8 mM) and 

i 

dipeptidyl peptidase IV (K = .0 mM). 

i 

,5-Dansyl-Glu-Gly-Arg 

Chloromethyl Ketone, 


251700 (1,5-DNS-GGACK, 2HCl) 

An effective irreversible inhibitor of Factor Xa (IC 50 = 00 nM) and 

urokinase. 

E-64 Protease Inhibitor 324890 An irreversible cysteine protease inhibitor that has no action on 

cysteine residues in other proteins. Specific active site titrant. 

Also inhibits the cysteine protease activity of GP 57/5 antigen of 

trypanosoma (IC = 00 nM). 

50 

E-64, Immobilized 324891 An immobilized form of the cysteine protease inhibitor E-64 

(Cat. No. 324890) covalently attached to hydrophilic acrylic beads via 

a 4-carbon spacer. Useful to affinity-precipitate cathepsins and other 

functionally related proteins from cell lysates or tissue extracts. 

Each set contains 25 mg of E-64 immobilized beads and 25 mg of 

control beads. 

mg $72 

mg $84 

5 mg $87 

mg $84 

mg $ 03 

28 Orders Phone 800 854 34 7 


Fax 800 776 0999 


5 mg 

0 mg 

25 mg 

$60 

$ 08 

$22 

0 mg $63 

500 mg $305 

0 mg $ 30 

g $266 

0 mg $84 

5 mg $ 22 

mg $ 00 

5 mg $20 

mg 

5 mg 

25 mg 

$34 

$ 35 

$509 

set $ 73



Proteases 


Ecotin, E. coli 330200 A potent, broad range inhibitor of serine proteases. Exhibits picomolar 

binding constant for the inhibition of chymotrypsin, elastase, Factor 

Xa, Factor XIIa, kallikrein, and trypsin. Also an effective inhibitor of 

collagenase and Granzyme B. 

EDTA, Disodium Salt, Dihydrate, 

Molecular Biology Grade 

324503 (Ethylenediaminetetraacetic Acid, 2Na) 

A reversible metalloprotease inhibitor. A chelator that may interfere 

with other metal ion-dependent biological processes. 

EDTA, Tetrasodium Salt 34103 (Ethylenediaminetetraacetic Acid, 4Na) 

A reversible metalloprotease inhibitor. A chelator that may interfere 

with other metal ion-dependent biological processes. 

EGTA 324625 [Ethyleneglycol-bis(b-aminoethyl)-N,N,N´,N´-tetraacetic Acid] 

A metalloprotease inhibitor. Highly useful for removal of heavy metal 

ions in biological systems. 

EGTA, Molecular Biology Grade 324626 [Ethyleneglycol-bis(b-aminoethyl)-N,N,N´,N´-tetraacetic Acid] 

A metalloprotease inhibitor. Highly useful for removal of heavy metal 

ions in biological systems. 

Elastase Inhibitor I 324692 (Boc-AAA-NHO-Bz; PPE Inhibitor) 

A serine protease inhibitor that inhibits pancreatic elastase 

(K i = 28 M - sec - ) and thermitase. 

Elastase Inhibitor II 324744 (HNE Inhibitor; MeOSuc-AAPA-CMK; MSACK) 

A potent inhibitor of human neutrophil elastase. 

Elastase Inhibitor III 324745 (HLE Inhibitor; MeOSuc-AAPV-CMK) 

A potent inhibitor of human neutrophil elastase (K i = 0 mM). 

00 mg $ 35 

00 g 

kg 

$32 

$ 3 

500 g $52 

0 g 

25 g 

g $50 

$46 

$79 

mg $92 

5 mg $98 

5 mg $ 04 

Elastatinal 324691 A competitive inhibitor of elastase (K i = 240 nM). 5 mg $85 

EST 330005 [E-64d; (2S,3S)-trans-Epoxysuccinyl-L-leucylamido-3-methylbutane Ethyl 

Ester; Loxistatin] 

A cell-permeable calpain inhibitor. Its action is similar to E-64 (Cat. No. 

324890); however, it is devoid of charged groups. 

FUT- 75 344960 (6-Amidino-2-naphthyl-4-guanidinobenzoate Dimethanesulfonate; 

Futhan; Nafamostat Mesylate) 

A synthetic broad-specificity serine protease inhibitor. Potently 

inhibits both coagulation and complement proteinases (C3a, C4a, and 

C5a) as well as Granzyme A. Inhibits Factor VIIa-mediated, Factor Xa 

generation (IC 50 = 00 nM). 

GGACK 347436 (Glu-Gly-Arg-chloromethyl Ketone) 

An irreversible inhibitor of urokinase (IC 50 =80 mM). 

2-Guanidinoethyl- 

mercaptosuccinic Acid 

369334 (GEMSA) 

Potent inhibitor of a carboxypeptidase B-like processing enzyme 

referred to as enkephalin convertase (K i = 8.8 nM). Ideal for use in affinity 

chromatography of the enzyme. 

HDSF 373250 (Hexadecylsulfonyl Fluoride) 

A substrate analog of phenylmethylsulfonyl fluoride (PMSF) that acts as 

an irreversible inhibitor of the lysosomal lipolytic enzyme, palmitoylprotein 

thioesterase- (PPT ) (IC = 25 mM) by modifying an active 

50 

site serine (Ser 5 ) in the enzyme. 

HIV Protease Inhibitor 382135 A potent HIV protease inhibitor (IC = 900 nM) that acts by binding to 

50 

the active site of the HIV protease. Also inhibits cathepsin D (IC = 50 

37 mM) and pepsin (IC = 00 mM) at high concentrations. 

50 

a-Iodoacetamide 407710 An irreversible inhibitor of several cysteine proteases. 

Useful for alkylating cysteine and methionine residues. 

(Z-LL) 2 Ketone 421050 (1,3-di-(N-Carboxybenzoyl-L-leucyl-L-leucyl)amino Acetone) 

A novel cysteine protease inhibitor that specifically and efficiently 

inhibits processing of the p-Prl signal peptide (IC 50 ~50 nM) without 

affecting the activities of signal peptidases and other proteases such as 

lysosomal cathepsins and proteasomes. 

mg $96 

5 mg $ 42 

5 mg $ 45 

5 mg $ 43 

25 mg 

00 mg 

$45 

$ 46 

mg $77 

25 g $90 

5 mg $73 


Phone 800 628 8470 


29

Proteases 



Kininogen, High Molecular Weight, 

Single Chain, Human Plasma 

Kininogen, High Molecular 

Weight, Two Chain, Human 

Plasma 

Kininogen, Low Molecular 

Weight, Human Plasma 

422686 (HMWK, Fitzgerald factor) 

Synthesized as a single polypeptide chain in the liver and secreted into 

the plasma, where it complexes with prekallikrein and factor XI. A nonenzymatic 

cofactor of the contact activation system. 

422688 Two-chain kinin-free kininogen prepared by kallikrein digestion of 

kininogen, which is then re-purified to remove traces of kallikrein. Binds 

to papain and cathepsin S with high affinity, exhibiting 2: binding 

stoichiometry. 

422685 (L-Kininogen) 

A multi-functional plasma protein that functions as a cysteine protease 

inhibitor. A non-enzymatic cofactor of the contact activation system. 

Leuhistin 432077 [((2R,3S)-3-Amino-2-hydroxy-2-(1H-imidazol-4-ylmethyl)-5-methyl)-5methylhexanoic 

Acid] 

A microbial product that competitively inhibits aminopeptidase M 

(K = 230 nM). 

i 

Leupeptin, Hemisulfate 108975 (Ac-LLR-CHO, ½H SO ; Ac-Leu-Leu-Arginal) 

2 4 

A reversible inhibitor of trypsin-like proteases and cysteine proteases. 

a 2 -Macroglobulin, Human Plasma 441251 (a 2 M; a 2 MG) 

A broad-range irreversible protease inhibitor. Forms “trap” around most 

proteases. 

DL-2-Mercaptomethyl-3guanidinoethylthiopropanoic 

Acid 

a -PDX, Human, Recombinant, 

E. coli 

445825 (Plummer’s Inhibitor) 

A potent and reversible inhibitor of human plasma carboxypeptidase N 

(K i = 2 nM). Also inhibits the hydrolysis of bradykinin. 

126850 (a 1 -Antitrypsin Portland) 

Recombinant protein derived from the bioengineered human a -antitrypsin 

gene fused to a His•Tag® sequence and a FLAG-tag. Contains 

a minimal furin consensus sequence, RXXR, that effectively blocks the 

furin-dependent processing of protein precursors (K i = 600 pM). 

Pepstatin A, Synthetic 516481 (Isovaleryl-Val-Val-4-amino-3-hydroxy-6-methylheptanoyl-Ala-4amino-3-hydroxy-6-methylheptanoic 

Acid; Iva-Val-Val-Sta-Ala-Sta) 

A reversible inhibitor of aspartic proteases. Inhibits cathepsin D, 

pepsin, and renin. 

Phenylmethylsulfonyl Fluoride 52332 (Benzylsulfonyl Fluoride; PMSF) 

An irreversible inhibitor of serine proteases. Its mechanism of action 

is analogous to that of diisopropylfluorophosphate. PMSF causes 

sulfonylation of the active-site serine residues. 

Phosphoramidon, Disodium Salt 525276 [N-a-Rhamnopyranosyloxyhydroxyphosphinyl)-L-leucyl-L-tryptophan, 

2Na] 

A highly specific inhibitor of thermolysin. Inhibits the conversion of big 

endothelin- to endothelin (IC = 4.6 mM). 

50 

PPACK, Dihydrochloride 520222 (D-Phe-Pro-Arg-Chloro-methylketone, 2HCl) 

A potent and selective inhibitor of thrombin. Specifically alkylates an 

active center histidine and thus is classified as an affinity label for 

thrombin. 

PPACK Dihydrochloride, 

Biotinylated 

520224 (Biotin-X-D-Phe-Pro-Arg-chloromethylketone, 2HCl) 

Biotin-X-analog of Cat. No. 520222. Specific probe for active serine 

proteases. Potent inhibitor of thrombin and tissue plasminogen activator 

(tPA). Useful for Western blot analyses of Factor VIIa, Factor XIa, 

thrombin, and tPA. 

mg $366 

mg $333 

00 mg $2 6 

5 mg $29 

5 mg 

0 mg 

25 mg 

50 mg 

00 mg 

mg 

0 mg 

30 Orders Phone 800 854 34 7 


Fax 800 776 0999 


$46 

$69 

$ 37 

$238 

$394 

$73 

$487 

00 mg $83 

2.5 mg $372 

5 mg 

25 mg 

00 mg 

g 

5 g 

25 g 

$38 

$ 3 

$334 

$28 

$52 

$ 56 

5 mg $ 44 

5 mg 

25 mg 

$ 48 

$504 

mg $380 

PPACKII, Trifluoroacetate Salt 520219 A potent and irreversible inhibitor of plasma and glandular kallikreins. 0 mg $ 65


Selection Guide for the Use of Specialized Protease Inhibitor Cocktails 

Product Cat. No. Recommended Application 

Protease Inhibitor Cocktail Set I 539 3 General use 

Protease Inhibitor Cocktail Set I, Animal-Free 535 42 General use (animal-free) 

Protease Inhibitor Cocktail Set II 539 32 Bacterial cell extracts 


Proteases 


Prolyl Endopeptidase Inhibitor II 537011 (Z-PP-CHO) 

A cell-permeable dipeptide aldehyde that acts as a specific, potent, slow 

and tight-binding transition state analog inhibitor of prolyl endopeptidase 

(K = 350 pM and 500 pM for mouse brain and human brain prolyl endo- 

i 

peptidase, respectively). 

TLCK, Hydrochloride 616382 (N a -Tosyl-Lys-Chloromethylketone, HCl) 

An irreversible inhibitor of trypsin-like serine proteases. Inactivates 

trypsin, specifically and irreversibly. Does not have any significant 

inhibitory effect on chymotrypsin. 

TPCK 616387 (N a -Tosyl-Phe-Chloromethylketone) 

An irreversible inhibitor of chymotrypsin. Useful for inhibiting 

chymotrypsin activity in trypsin preparations. 

Tripeptidylpeptidase II Inhibitor 645905 (H-AAF-CMK, TFA; TPPII Inhibitor) 

A serine protease inhibitor that acts as a potent, selective, dosedependent, 

and irreversible inhibitor of tripeptidylpeptidase II. 

Achieves about 80% inhibition of TPPII in vitro at 0 mM. 

Protease Inhibitor Cocktail Set III, EDTA-Free 539 34 Mammalian cells and tissue extracts, immobilized metal 

affinity chromatography 

Protease Inhibitor Cocktail Set III, Animal-Free 535 40 Mammalian cells and tissue extracts (animal-free) 

Protease Inhibitor Cocktail Set IV 539 36 Fungal and yeast cell extracts 

Protease Inhibitor Cocktail Set V, EDTA Free 539 37 Mammalian cells and tissue extracts 

Protease Inhibitor Cocktail Set V, Animal-Free 535 4 Mammalian cells and tissue extracts (animal-free) 

Protease Inhibitor Cocktail Set VI 539 33 Plant cell extracts 

Protease Inhibitor Cocktail Set VII 539 38 Purification of proteins containing His•Tag® sequences 

Protease Inhibitor Cocktail Set VIII 539 29 Broad range cysteine protease inhibition 

Serine Protease Inhibitor Cocktail Set I 565000 Broad range serine protease inhibition 

5 mg $ 24 

50 mg 

250 mg 

250 mg 

g 

$38 

$ 24 

$39 

$ 0 

5 mg $72 

Trypsin Inhibitor, Corn 650345 A specific inhibitor of human factor XIIa. mg $209 

Trypsin Inhibitor, Soybean 65035 A reversible serine protease inhibitor. Inhibits factor Xa, trypsin, 

chymotrypsin, kallikrein, and plasmin. 

Trypsin Inhibitor, Soybean, High 

Activity 

D-Val-Phe-Lys Chloromethyl 

Ketone, Dihydrochloride 

650357 A reversible serine protease inhibitor. Inhibits factor Xa, trypsin, 

chymotrypsin, kallikrein, and plasmin. 

627624 (Plasmin Inhibitor, 2HCl) 

Selective irreversible inhibitor of plasmin with high selectivity for 

plasmin over urokinase. 

00 mg 

g 

00 mg 

250 mg 

$55 

$273 

$70 

$ 53 

5 mg $ 35 


Phone 800 628 8470 


3

Proteases 

Protease Inhibitor Cocktails 

Protease Inhibitor Cocktail Set I 

A cocktail containing five protease inhibitors that will inhibit a broad range of proteases. Reconstitute each vial with ml 

H 2 O to obtain a 00x stock solution. When diluted, x stock solution contains the indicated amount of inhibitors. 

Cat. No. 539131 1 vial $28 

10 vials $202 

Protease Inhibitor Cat. No. 1x Concentration Target Protease 

AEBSF, Hydrochloride 101500 500 mM Serine Proteases 


Crystalline 

619370 50 nM Serine Proteases and Esterases 

E-64 Protease Inhibitor 324890 mM Cysteine Proteases 

EDTA, Disodium 324503 500 mM Metalloproteases 

Leupeptin, Hemisulfate 108975 mM Cysteine Proteases and Trypsin-like Proteases 

Protease Inhibitor Cocktail Set II 

This cocktail is recommended for use with bacterial cell extracts. Cocktail contains five protease inhibitors with broad 

specificity for the inhibition of aspartic, cysteine, serine, and metalloproteases as well as aminopeptidases. Reconstitute 

each vial with ml DMSO and 4 ml H 2 O to obtain a 5 ml stock solution. When reconstituted, each vial will contain the 

following amount of inhibitors. Note: set = vial of lyophilized protease inhibitor cocktail and vial DMSO, ml. 

Cat. No. 539132 1 set $75 

5 sets $296 

Protease Inhibitor Cat. No. Concentration in 

the Vial 

Target Protease 


Bestatin 200484 .7 mM Aminopeptidase B and Leucine Aminopeptidase 

E-64 Protease Inhibitor 324890 200 mM Cysteine Proteases 

EDTA, Disodium 324503 500 mM Metalloproteases 

Pepstatin A 516481 2 mM Aspartic Proteases 

Protease Inhibitor Cocktail Set III 

This cocktail is recommended for use with mammalian cells and tissue extracts. Cocktail contains six protease inhibitors 

(in ml of DMSO) with broad specificity for the inhibition of aspartic, cysteine, and serine proteases as well as aminopeptidases. 

Each vial contains the following amount of inhibitors. One ml is sufficient for 20 g of tissue. 

Cat. No. 539134 1 ml $57 

1 set $248 

Protease Inhibitor Cat. No. Concentration in 

the Vial 

Target Protease 



Crystalline 

616370 80 mM Broad Spectrum, Serine Proteases 

Bestatin 200484 5 mM Aminopeptidase B and Leucine Aminopeptidase 

E-64 Protease Inhibitor 324890 .5 mM Cysteine Proteases 

Leupeptin, Hemisulfate 108975 2 mM Cysteine Proteases and Trypsin-like Proteases 

Pepstatin A 516481 mM Aspartic Proteases 

32 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Protease Inhibitor Cocktails, continued 

Protease Inhibitor Cocktail Set IV 

This cocktail is recommended for fungal and yeast cell extracts. Cocktail contains four protease inhibitors (in ml of 

DMSO) with broad specificity for the inhibition of aspartic-, cysteine-, metallo-, and serine-proteases. Each vial contains 

the following amount of inhibitors. 

Cat. No. 539136 1 ml $52 


1 set $190 

Protease Inhibitor Cat. No. Concentration in the Vial Target Protease 


E-64 Protease Inhibitor 324890 .5 mM Cysteine Proteases 


o-Phenanthroline 516705 500 mM Metalloproteases 

Protease Inhibitor Cocktail Set V, EDTA-Free 

$ 90 

$52 

A cocktail containing four protease inhibitors for the inhibition of serine, cysteine, but not metalloproteases. 

Reconstitute each vial with ml H O to obtain a 00x stock solution. When diluted to x stock solution, the set will contain 

2 

the following amount of inhibitors. 

Cat. No. 539137 10 vials $203 

Protease Inhibitor Cat. No. 1X Concentration Target Protease 



Crystalline 

616370 50 nM Broad-Spectrum, Serine Proteases 

E-64 Protease Inhibitor 324890 mM Cysteine Proteases 

Leupeptin, Hemisulfate 108975 mM Cysteine Proteases and Trypsin-like Proteases 

Protease Inhibitor Cocktail Set VI 

A cocktail of six protease inhibitors with broad specificity for the inhibition of aspartic, cysteine, serine, and metalloproteases 

as well as aminopeptidases. This cocktail is recommended for use with plant cell extracts. 

Cat. No. 539133 1 ml $62 

1 set (5 x 1 ml) $267 

Protease Inhibitor Cat. No. Concentration in the Vial Target Protease 


Bestatin 200484 0 mM Aminopeptidase B and Leucine Aminopeptidase 

E-64 Protease Inhibitor 324890 3 mM Cysteine Proteases 

Leupeptin, Hemisulfate 108975 2 mM Cysteine Proteases and Trypsin-like Proteases 

o-Phenanthroline 516705 500 mM Metalloproteases 


Proteases 


Phone 800 628 8470 


33

Proteases 

Protease Inhibitor Cocktails, continued 

Protease Inhibitor Cocktail Set VII 

This cocktail is recommended for purification of proteins containing His•Tag® sequences. Cocktail contains five protease 

inhibitors (in ml DMSO) with broad specificity for the inhibition of cysteine, serine, aspartic, and thermolysinlike 

proteases and aminopeptidases. One ml is recommended for the inhibition of proteases in 0 g cells. 

Cat. No. 539138 1 ml $62 

1 set (5 x 1 ml) $267 

Protease Inhibitor Cat. No. Mol. Wt. Concentration in the Vial Target Protease 

AEBSF, Hydrochloride 101500 239.5 00 mM Serine Proteases 

Bestatin 200484 308.4 5 mM Aminopeptidase B and Leucine 

Aminopeptidase 

E-64 Protease Inhibitor 324890 357.4 .5 mM Cysteine Proteases 

Pepstatin A 516482 685.9 2 mM Aspartic Proteases 

Phosphoramidon 525276 587.5 200 mM Metalloendopeptidases 

Protease Inhibitor Cocktail Set VIII 

A DMSO solution of three protease inhibitors with selective specificity for the inhibition of cysteine proteases, 

including calpains, cathepsins, and papain. 

Cat. No. 539129 1 ml $63 

1 set (5 x 1 ml) $268 

Protease Inhibitor Cat. No. Mol. Wt. Concentration in the Vial Target Protease 

ALLN 208719 383.5 .56 mM Calpain I/II, Cathepsin B, 

Cathepsin L, Cysteine Proteases 

Cathepsin Inhibitor I 219415 475.5 500 mM Cathepsin B, Cathepsin L, 

Cathepsin S, Papain 

E-64 Protease Inhibitor 324890 357.4 .5 mM Cysteine Proteases 

Protease Arrest Reagent 

An optimized concentration of various reversible and irreversible 

inhibitors to inhibit serine, cysteine, and calpain proteases. Suitable for 

the protection of proteins purified from animal tissues, plant tissues, 

yeast, and bacteria. Protease Arrest Reagent is provided as a 50x 

solution that when diluted in extraction buffer at pH 7.0 to 8.0 inhibits 

95-98% of protease activity. EDTA is also provided separately to inhibit 

metalloproteinases. 

Cat. No. 539124 1 set $150 

Protease Inhibitor Set 

A set of 6 vials. Each set contains 50 mg of AEBSF, HCl (Cat. No. 

0 500), mg of E-64 (Cat. No. 324890), mg of EST (E-64d; Cat. No. 

330005), 5 mg of Leupeptin, Hemisulfate (Cat. No. 08975), 5 mg of 

Pepstatin A (Cat. No. 5 6482), 50 mg of TLCK, HCl (Cat. No. 6 6382), 

and 250 mg of TPCK (Cat. No. 6 6387). 

Cat. No. 539128 1 set $274 

Serine Protease Inhibitor Cocktail Set I 

A cocktail of four protease inhibitors that is useful for inhibition of a 

broad range of serine proteases. Reconstitute each vial with ml of 

H 2 O to obtain a 00x stock solution. x stock solution contains 

500 mM AEBSF, HCl (Cat. No. 0 500), 420 nM Aprotinin (Cat. No. 

6 6370), 20 mM Elastatinal (Cat. No. 32469 ), and mM GGACK (Cat. 

No. 347436). 

Cat. No. 565000 1 vial 

5 vials 

34 Orders Phone 800 854 34 7 


Fax 800 776 0999 


$60 

$239

N Animal-Free Protease Inhibitor Cocktail Sets 

Protease Inhibitor Cocktail Set I, 

Animal-Free 

A cocktail of five protease inhibitors for the inhibition of a broad 

range of proteases and esterases. Each vial, when reconstituted with 

ml H 2 O, yields a 00X stock solution. When diluted to X the cocktail 

contains 500 mM AEBSF, HCl (Cat. No. 0 500), 50 nM Aprotinin, 

recombinant (Cat. No. 6 637 ), mM E-64 (Cat. No. 324890), 

500 mM EDTA, Disodium Salt and mM Leupeptin Hemisulfate (Cat. No. 

08975). Available as ml vial or as a set of 0 x ml. 

Cat. No. 535142 1 ml 

1 set 

Protease Inhibitor Cocktail Set III, 

Animal-Free 

A cocktail of six protease inhibitors with broad specificity for 

the inhibition of aspartic, cysteine, and serine proteases as well as 

aminopeptidases. This cocktail is recommended for use with 

mammalian cell and tissue extracts. Each vial contains 00 mM AEBSF, 

HCl (Cat. No. 0 500), 80 mM Aprotinin, Recombinant (Cat. No. 6 637 ), 

5 mM Bestatin (Cat. No. 200484), .5 mM E-64 (Cat. No. 324890), 2 mM 

Leupeptin Hemisulfate (Cat. No. 08975), and mM Pepstatin A 

(Cat. No. 5 6482). Available as ml vial or a set of 5 x ml. 

Cat. No. 535140 1 ml 

1 set 

Protease Inhibitor Cocktail Set V, 

Animal-Free 


$28 

$202 

$57 

$245 

A cocktail of four protease inhibitors for the inhibition of serine 

and cysteine proteases, but not metalloproteases. Each vial, when 

reconstituted with ml H 2 O, will yield a 00X stock solution. 

When diluted to X the cocktail contains 500 mM AEBSF, HCl 

(Cat. No. 0 500), 50 nM Aprotinin, recombinant (Cat. No. 6 637 ), 

mM E-64 (Cat. No. 324890), and mM Leupeptin Hemisulfate (Cat. No. 

08975). Available as ml vial or set of 0 x ml. 

Cat. No. 535141 1 ml 

1 set 

$57 

$245 

Now with 

FAQs 

Proteases 


Phone 800 628 8470 


35

Proteases 

Proteasome and Ubiquitination Inhibitors 

Proteasomes are large multi-subunit complexes, 

localized in the nucleus and cytosol that selectively 

degrade intracellular proteins. A protein marked for 

degradation is covalently attached to multiple molecules 

of ubiquitin (Ubq). Four or more Ubq are required to 

set a protein for degradation by the proteasome. Ubq 

is a highly conserved 76-amino acid (8.6 kDa) protein, 

which escorts proteins for rapid hydrolysis to the multicomponent 

enzymatic complex, the 26S proteasome. The 

proteolytic core of this complex, the 20S proteasome, 

contains multiple peptidase activities and functions 

as the catalytic machine. This core is composed of 28 

subunits arranged in four heptameric, tightly stacked, 

rings (a 7 , b 7 , b 7 , a 7 ) to form a cylindrical structure. The 

a-subunits make up the two outer and the b-subunits the 

two inner rings of the stack. The entrance of substrate 

proteins to the active site of the complex is guarded 

by the a-subunits that allow access only to unfolded 

and extended polypeptides. The proteolytic activity is 

confined to the b-subunits. The 19S complex “caps” at 

each end of the 20S proteasome help in unfolding protein 

substrates. The 19S cap contains subunits with ATPase 

activity, subunits that recognize and bind polyubiquitin 

chains and putative unfoldases that unfold protein 

chains and translocate them into the 20S proteasome. 

In the Ubq-proteosome degradation pathway, Ubq is 

first covalently ligated to target proteins by a multienzymatic 

system consisting of Ubq-activating (E1), 

Ubq-conjugating (E2), and the Ubq-ligating (E3) 

enzymes. The E1 activates a Ubq monomer at its Cterminal 

cysteine residue to a high-energy thioester 

bond which is then transferred to a reactive cysteine 

residue of the E2 enzyme. The final transfer of Ubq 

to the h-amino group of a reactive lysine residue of 

substrate proteins is brought about by the E3 enzyme. 

Ubiquitinated protein is then escorted to the 26S 

proteasome where it undergoes final degradation and 

the ubiquitin is released and recycled. The ubiquitinproteasome 

system plays a major role in the degradation 

of many proteins involved in cell cycle, proliferation, 

and apoptosis. Proteasomes also breakdown abnormal 

proteins that result from oxidative stress and 

mutations that might otherwise disrupt normal cellular 

homeostasis. This pathway has been implicated in 

several forms of malignancy, in the pathogenesis of 

several genetic diseases, and in the pathology of muscle 

wasting. It is also involved in the destruction of proteins 

that participate in cell cycle progression, transcription 

control, signal transduction, and metabolic regulation. 

Several distinct groups of compounds, designed to act as 

selective proteasome inhibitors, have helped immensely 

in understanding the biological role and importance of 

the ubiquitin-proteasome pathway. These compounds are 

designed to block proteasome function in cancer cells 

without significantly affecting biological processes in 

the normal cell. 

References: 

Spano, J.P. et al. 2005, Bull. Cancer 92, 945. 

Mistiades, C.S. et al. 2005. Essays Biochem. 41, 205. 

Magill, L., et al. 2003. Hematology 8, 275. 

Voorhees, P.M., et al. 2003. Clin. Cancer Res. 9, 63 6. 

Kroll, M., et al. 999. J. Biol. Chem. 274, 794 . 

Koegl, M., et al. 999. Cell 96, 635. 

Schwartz, A.L., and Ciechanover, A. 999. Annu. Rev. Med. 50, 57. 

Gerards, W.L.H., et al. 998. Cell. Mol. Life Sci. 54, 253. 

Spataro, V., et al. 998. Br. J. Cancer 77, 448. 

Jensen, D.E., et al. 998. Oncogene 16, 097. 

Pickart, C.M. 997. FASEB J. 11, 055. 

Bogyo, M., et al. 997. Biopolymers 43, 269. 

Coux, O., et al. 996. Annu. Rev. Biochem. 65, 80 . 

Maupin-Furlow, J.A., and Ferry, J.G. 995. J. Biol. Chem. 270, 286 7. 

Jensen, T.J., et al. 995. Cell 83, 29. 

Ciechanover, A. 994. Cell 79, 3. 

More online... www.calbiochem.com/inhibitors/Ubq 

36 Orders Phone 800 854 34 7 


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Proteasome and Ubiquitination Pathway Inhibitors 

Product Cat. No. 


Proteases 

Cellpermeable? 

Reversible? Comments Size Price 

AdaAhX 3 L 3 VS 114802 Yes No Inhibits chymotrypsin-like (IC 50 = 0.05–0.0 mM), trypsinlike 

(IC 50 = .0–5.0 mM), and PGPH (IC 50 = 0.5– .0 mM) 

activities of the 20S proteasome. 

AdaLys(bio)AhX 3 L 3 VS 114803 Yes No Inhibits chymotrypsin-like (IC 50 = 0.05–0. mM), trypsinlike 

(IC 50 = 5.0– 0.0 mM), and PGPH (IC 50 = 2.0–5.0 mM) 

activities of the 20S proteasome in living cells. Useful for 

the detection of catalytic b-subunits of both constitutive 

proteasome and immunoproteasome through Western 

blotting. 

ALLN 

(Calpain Inhibitor I) 

208719 Yes Yes Inhibits chymotrypsin-like activity of the proteasome 

(K i = 5.7 mM). Also inhibits calpain I, calpain II, cathepsin B, 

and cathepsin L. 

Epoxomicin, Synthetic 324800 Yes No Inhibits chymotrypsin-like, trypsin-like and peptidylglutamyl 

peptide hydrolyzing (PGPH) activities of the proteasome. 

N InSolution Epoxomicin, 

Synthetic 

324801 Yes No A mM (50 mg/90 ml) solution of Epoxomicin, Synthetic 


Hdm2 E3 Ligase Inhibitor 373225 Yes Yes A cell-permeable, reversible inhibitor of hdm2 E3 ligase 

that is shown to block hdm2-mediated ubiquitination of 

p53 (IC 50 = 2.7 mM using Ub-Ubc4 as the donor substrate). 

The inhibition is non-competitive with respect to either the 

donor or acceptor substrate. 

Lactacystin, Synthetic 426100 Yes No A potent and selective proteasome inhibitor. Inhibits the 

chymotryptic-and tryptic-like peptidase activities of 

proteasomes. Also inhibits cathepsin A. 

clasto-Lactacystin-blactone 

426102 Yes No A potent and selective proteasome inhibitor. Inhibits the 

chymotrypsin and trypsin-like peptidase activities of 

proteasomes. Also inhibits cathepsin A. 

a-Methylomuralide 426104 Yes No An a-methyl analog of clasto-Lactacystin b Lactone (Omuralide, 

Cat. No. 426 02) that displays improved hydrolytic 

stability. Reported to be a potent, selective, and irreversible 

inhibitor of proteasome function (k inact chymotrypsin-like 

peptidase activity of purified 20S proteasome from bovine 

brain = 2300 M - s - for a-Methylomuralide vs. 3060 M - s - 

for Omuralide). 

MG- 5 

(Z-LLNva-CHO) 

MG- 32 

(Z-LLL-CHO) 

474780 Yes Yes Potent proteasome inhibitor (IC 50 = 2 nM and 35 nM 

for 20S and 26S proteasomes, respectively). Inhibits 

chymotrypsin-like activity of the proteasomes. 

474790 Yes Yes Inhibits chymotrypsin-like activity of the proteasomes 

(K i = 4 nM). 

InSolution MG- 32 474791 Yes Yes Supplied as a 0 mM ( mg / 2 0 ml) solution of MG- 32 

(Cat. No. 474790) in anhydrous DMSO. 

NLVS 482240 Yes No Inhibits chymotrypsin-like, trypsin-like, and peptidylglutamyl-peptidase 

activities of proteasomes. 

NP-LLL-VS 492025 Yes No An intermediate that can be used to prepare radiolabeled 

25 I–NIP–L3 VS for proteasome inhibition studies. NIP-L 3 VS 

acts by covalently modifying the active site threonine of 

the catalytic b-subunit of the proteasome. 

Proteasome Inhibitor I 

(PSI) 

250 mg $207 

250 mg $207 

5 mg 

25 mg 

$48 

$ 72 

00 mg $ 84 

50 mg $ 0 

5 mg $73 

200 mg $237 

00 mg $ 98 

00 mg $20 

5 mg $ 43 

mg 

5 mg 

$34 

$98 

mg $39 

500 mg $227 

500 mg $ 96 

539160 Yes Yes Inhibits chymotrypsin-like activity of the proteasome. mg 

5 mg 

$68 

$202 


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37

Proteases 

Proteasome and Ubiquitination Inhibitors, continued 

Product Cat. No. 

N InSolution Proteasome 


Proteasome Inhibitor II 

(Z-LLF-CHO) 

Proteasome Inhibitor III 

[Z-LLL-B(OH) 2 ] 

Proteasome Inhibitor IV 

(Z-GPFL-CHO) 

N Proteasome Inhibitor VII, 

Antiprotealide 

Cellpermeable? 

Reversible? Comments Size Price 

539161 Yes Yes A 50 mM (5 mg/ 62 ml) solution of Proteasome Inhibitor I 



(K i = 460 nM). 


(K i = 30 nM). 

539175 Yes Yes K i s = .5 mM for branched chain amino acid preferring, 

2.3 mM for small neutral amino acid preferring, and 40.5 

mM for chymotrypsin-like activities; IC 50 = 3. mM for PGPH 

activity. Only weakly inhibits trypsin-like proteasomal 

activity. 

539179 Yes No An Omuralide-Salinosporamide hybrid that irreversibly 

inactivates the b5-subunit of the human 20S proteasome. 

Shown to be ~2.5-fold more potent than Omuralide (Cat. No. 

426 02) and somewhat less potent than Salinosporamide A. 

Ro 06-9920 557550 Yes No A highly selective, irreversible inhibitor of IkBaee ubiquitination 

(IC 50 = 2.3 mM). Blocks NF-kB-dependent cytokine 

expression in human PBMNs (IC 50 ~700 nM for TNF-a, 

IL- b, and IL-6 inhibition) and rats. 

Ro 06-9920, Control 557551 Yes — A negative control compound for Ro 06-9920 (Cat. No. 

557550) (IkBaee ubiquitination IC 50 >80 mM). 

Tyropeptin A, Synthetic 657008 Yes Yes Inhibitor of chymotrypsin-like (IC 50 = 00 ng/ml) and trypsin-like 

(IC 50 = .5 mg/ml) activities of the proteasome. No 

effect on PGPH activity even at a concentration of 

00 mg/ml. 

Ubiquitin Aldehyde 662056 No Yes Potent and specific inhibitor of multiple ubiquitin 

hydrolases involved in pathways of intracellular protein 

modification and turnover. 

UCH-L Inhibitor 662086 Yes Yes A potent, reversible, competitive, and active site-directed 

inhibitor of UCH-L (K i = 400 nM; IC 50 = 880 nM) with 

~28-fold greater selectivity over UCH-L3 (Cat. No. 662090). 

UCH-L3 Inhibitor 662089 Yes No A selective and potent inhibitor of UCH-L3 (IC 50 =600 nM) with 

~ 25-fold greater selectivity over UCH-L (IC 50 = 75 mM). 

Proteasome Inhibitor Set I 

A set of three vials. Each set contains mg of Proteasome Inhibitor I 

(Cat. No. 539 60), 200 mg of Lactacystin (Cat. No. 426 00), and mg 

of MG- 32 (Cat. No. 474790). 

Cat. No. 539164 1 set $299 

Proteasome Inhibitor Set II 

A set of three vials. Each set contains 5 mg of ALLN (Cat. No. 2087 9), 

00 mg each of Epoxomicin (Cat. No. 324800), and clasto-Lactacystin 

b-Lactone (Cat. No. 426 02). 

Cat. No. 539165 1 set $313 

The Ubiquitin- 

Proteasome 

Pathway 

A comprehensive 

collection of 

research products 

Order your 

FREE copy 

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5 mg $202 

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$64 

$ 90 

00 mg $20 

5 mg $ 68 

50 mg $ 80 

mg 

5 mg 

$72 

$25 

mg $67 

mg $60 

50 mg $ 90 

0 mg $93 

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Transmembrane receptors of various hormones are 

coupled to adenylate cyclase (AC) via heterotrimeric 

G-proteins. Ligand binding to the receptor changes the 

receptor conformation, allowing it to associate with a 

G-protein. This results in the activation of the specific 

G-protein via exchange of GTP for GDP bound to the asubunit 

of the G-protein. The activated G-protein in turn 

activates AC resulting in the conversion of ATP to cAMP. 

cAMP then acts to regulate a wide variety of cellular 

processes. AC can couple with both the stimulatory and 

inhibitory G-proteins (G s and G i ). Interaction with G s 

stimulates its activity and interaction with G i inhibits its 

enzymatic activity. 

At least nine different isoforms of AC have been 

reported that differ in their regulatory properties and 

are differentially expressed in various tissues. They 

are integral membrane proteins that are composed of 

two cytoplasmic domains and two membrane-spanning 

domains, each of which contains six transmembrane 

spans. The amino acid sequence of each cytoplasmic 

domain, which is thought to contain a nucleotide (ATP) 

binding site, is well conserved among the various 

subtypes. Although ACs can exist in both particulate 

and soluble forms, the particulate form is more 

prevalent in mammals. Based on the conservation 

of their catalytic domains, three classes of ACs are 

described: class I-ACs are found in Gram-negative 

facultative anaerobes, such as E. coli; class II-“toxic' 

ACs, including calmodulin (CaM)-activated ACs 

are found in pathogenic bacteria, such as Bordetella 


Other Inhibitors of Biological Interest 


Adenylate Cyclase Inhibitors 

Adenylate Cyclase Inhibitors 

pertussis and Bacillus anthracis; and class III-ACs are 

found in a wide variety of organisms ranging from 

bacteria to human. Class III-AC also include nine 

isoforms found in mammals, which are designated AC- 

1 to AC-9. These nine isoforms are stimulated by the 

a-subunit of G s -protein and by forskolin. ACs are also 

capable of receiving signals from a variety of other 

sources, such as G i -a, protein kinase A, C, CaM kinase, 

and Ca 2+ /CaM. Hormonal activation of CaM-dependent 

adenylate cyclase occurs at very low Ca 2+ levels. The 

activity of AC is inhibited by high levels of Ca 2+ , which 

also activates CaM-dependent phosphodiesterase. 

References: 

Insel, P.A., and Ostrom, R.S. 2003. Cell. Mol. Neurobiol. 23, 305. 

Cui, H., and Green, R. D. 200 . Biochem. Biophys. Res. Comm. 283, 07. 

Schwartz, J.H. 200 . Proc. Natl. Acad. Sci. USA 98, 3482. 

Sunahara, R.K., et al. 996. Annu. Rev. Pharmacol. Toxicol. 36, 46 . 

MacNeil, S., et al. 985. Cell Calcium 6, 2 3. 


Adenylyl Cyclase Toxins Inhibitor 116845 (Ethyl-5-aminopyrazolo[1,5-a]quinazoline-3-carboxylate) 

A cell-permeable inhibitor of adenylate cyclase (IC 50 = 90 mM). 

Adenylyl Cyclase Type V Inhibitor, 

NKY80 

More online... www.calbiochem.com/inhibitors/AC 

116850 [2-Amino-7-(furanyl)-7,8-dihydro-5(6H)-quinazolinone] 

A cell-permeable, potent and selective inhibitor of adenylyl cyclase 

(AC) type V isoform (IC 50 = 8 .3 mM, 32 mM and .7 mM for type V, 

III, and II, respectively) in the presence of Gsx GTPrs-Forskolin. 

Angiotensin II, Human 05-23-0101 (DRVYIHPF) 

An inhibitor of adenylate cyclase activity in spontaneously 

hypertensive rats. 

2',5'-Dideoxyadenosine 288104 (2',5'-dd-Ado) 

A cell-permeable, non-competitive inhibitor of adenylate cyclase 

(IC 50 = 3 mM). Binds to the adenosine binding site. 

0 mg $ 00 

5 mg 

25 mg 

mg 

5 mg 

25 mg 

$60 

$2 

$23 

$34 

$ 35 

mg $53 


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39


Adenylate Cyclase Inhibitors, continued 


InSolution MANT-GppNHp 444168 {mant-GMPPNP; 2´/3´-O-(N-Methylanthraniloyl)-guanosine- 

5´-[(b,g)-imido]triphosphate, Triethylammonium Salt; 2´/3´-O- 

(N-Methylanthraniloyl)-b,g-imidoguanosine-5´-triphosphate, 

Triethylammonium Salt} 

Acts as a potent, competitive inhibitor of adenylyl cyclase 

(AC; K i = 6 nM and 55 nM in forskolin/Mn 2+ -stimulated AC in 

S49 cyc - membranes and insect cell membranes, respectively). 

Supplied as a 5 mM solution in H 2 O. 

InSolution MANT-GTPgS 444169 [2´/3´-O-(N-Methylanthraniloyl)-guanosine-5´-(g-thio)triphosphate, 

Triethylammonium Salt; 2´/3´-O-(N-Methylanthraniloyl)-gthioguanosine-5´-triphosphate, 

Triethylammonium Salt; mGTPgS] 

Acts as a potent, competitive inhibitor of adenylyl cyclase 

(AC; K i = 53 nM in forskolin/Mn 2+ -stimulated AC in S49 cyc - 

membranes). Supplied as a 5 mM solution in H 2 O. 

MDL- 2,330A, Hydrochloride 444200 [cis-N-(2-Phenylcyclopentyl)azacyclotridec-1-en-2-amine, HCl] 

A cell-permeable, irreversible inhibitor of adenylate cyclase 

(IC 50 = 250 mM). 

50 ml $220 

50 ml $220 

mg $38 

Melittin 444605 Inhibits adenylyl cyclase activity in synaptic membranes. 250 mg $67 

SQ 22536 568500 [9-(Tetrahydro-2´-furyl)adenine] 

A cell-permeable adenylate cyclase inhibitor. Blocks PTH-stimulated 

AC activity (IC 50 = 200 mM). 

5 mg $ 0 

40 Orders Phone 800 854 34 7 


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Angiotensin-Converting Enzyme (ACE) Inhibitors 

The renin-angiotensin system plays an important role in 

electrolyte balance and fluid regulation. ACE inhibitors 

have become important clinical tools in the management 

of hypertension. They block the activation of the 

renin-aldosterone system, thereby reducing peripheral 

Angiotensin-Converting Enzyme (ACE) Inhibitors 



vascular resistance. ACE inhibitors also improve 

myocardial oxygen consumption and cardiac output and 

moderate left ventricular and vascular hypertrophy. 


Captopril 211875 ([2S]-1-[3-Mercapto-2-methylpropionyl]-L-proline; SQ-14225) 

A competitive inhibitor of angiotensin converting enzyme 

(IC 50 = 23–35 nM). 

TAPI-2 579052 {N-(R)-[2-(Hydroxyaminocarbonyl)methyl]-4-methylpentanoyl-L-tbutyl-alanyl-L-alanine, 

2-aminoethyl Amide; TNF-a Protease Inhibitor- 

2} 

ATPase Inhibitors 

ATPase Inhibitors 

A hydroxamate-based inhibitor of MMPs and TACE. Also acts as a 

weak inhibitor of angiotensin converting enzyme (IC 50 = 8 mM). 

DL-Thiorphan 598510 N-[(RS)-2-Benzyl-3-mercaptopropanoyl]-glycine 

A thiol containing amido-acid that selectively binds to the active site 

zinc of metalloproteinases and blocks their activity (IC 50 = 2. nM 

for neutral endopeptidase-NEP). Reported to inhibit the activity of 

angiotensin-converting enzyme (ACE) at much higher concentrations 

(IC 50 = 4 mM); however, it does not affect the activity of endothelinconverting 

enzyme. 

Aromatase Inhibitors 

Aromatase Inhibitors 

More online... www.calbiochem.com/inhibitors/ACE 

g $44 

mg $262 

0 mg $ 95 


Aromatase Inhibitor I 182540 A potent, competitive, nonsteroidal inhibitor of aromatase (P450arom; IC 50 = 40 nM for 

human aromatase). Reported to be more potent than fadrozole in inhibiting aromatase 

activity. Does not significantly inhibit 7a-hydroxylase. 

More online... www.calbiochem.com/inhibitors/ATPase 


Adenosine 1160 Exerts a biphasic effect on Ca 2+ - Mg 2+ -ATPase activity. Inhibits the 

activity at ~ 00 nM levels. 

Amiloride, Hydrochloride 129876 A potent and specific inhibitor of trans-membrane Na + entry and 

Na + /K + ATPase. Diminishes the urinary transepithelial potential 

difference and short-circuit current (IC 50 = 300 nM). 

Atrial Natriuretic Factor -28, Rat 05-23-0301 (rANF; SLRRSSCFGGRIDRIGAQSGLGCNSFRY) 

Reduces the activity of Na + -K + -ATPase in rat kidney and activates 

neuronal guanylate cyclase. 

0 g 

00 g 

mg $ 06 

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$ 5 

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4


ATPase Inhibitors, continued 


Bafilomycin A , Streptomyces 

griseus 

196000 A specific inhibitor of vacuolar-type H + -ATPase (V-type; K i = 500 pM) 

and serves as a valuable tool for distinguishing among different types 

of ATPases. 

BHQ 286888 [t-BuBHQ; 2,5-Di-(t-butyl)-1,4-hydroquinone] 

Mobilizes Ca 2+ from the IP 3 -sensitive stores by inhibiting microsomal 

and sarcoplasmic reticulum Ca 2+ -ATPase activity. Blocks the 

formation of prostaglandin E2 and prostacyclin (IC 50 = 0.5– .0 mM). 

(±)-Blebbistatin 203390 A cell-permeable, selective, potent, and reversible inhibitor of nonmuscle 

myosin II. Inhibits the ATPase and gliding motility of human 

platelets (≤ 00 mM). 

N InSolution Blebbistatin, Racemic 203389 A 50 mM (5 mg/342 ml) solution of (±)-Blebbistatin 


(—)-Blebbistatin 203391 The active enantiomer of (±)-Blebbistatin (Cat. No. 203390) that 

accounts for the inhibitory activity towards ATPase (IC ~2 mM) and 

50 

myosin II-dependent cellular processes. 

(+)-Blebbistatin 203392 The inactive enantiomer of Blebbistatin. Useful as a negative control 

for the active enantiomer (Cat. No. 20339 ). 

BTS 203895 (N-Benzyl-p-toluenesulphonamide) 

A potent inhibitor of Ca2+ -stimulated myosin S actin-stimulated 

ATPase activity (IC = ~5 mM). Also blocks actin-stimulated ATPase 

50 

activity with similar potency (IC = 5 mM). Reversibly blocks gliding 

50 

motility of skeletal muscle myosin (IC = 30 mM for H-Ras). 

50 

Bufalin 203900 [5b, 20(22)-Bufadienolide-3b, 14-diol] 

A cardiotonic steroid that potently inhibits ouabain-sensitive 

Na + ,K + -ATPase activity (IC 50 = .4 nM). 

2,3-Butanedione 2-Monoxime 203984 (BDM) 

A general reversible inhibitor of myosin ATPases of eukaryotic cells. 

Calmidazolium Chloride 208665 (Compound R 24571) 

A calmodulin antagonist that also acts as a strong, non-competitive 

inhibitor of skeletal muscle sarcoplasmic reticulum Ca 2+ -ATPase (K i = 

60 nM). 

Cyclopiazonic Acid, Penicillium 

cyclopium 

239805 (CPA) 

A cell-permeable, reversible inhibitor of endoplasmic reticulum Ca 2+ - 

ATPase (IC 50 = 0 -20 nM). 

DPC 300265 (Diphenylamine-2-carboxylic Acid; 2,2´-Iminodibenzoic Acid; N- 

Phenylanthranilic Acid) 

A potent non-specific blocker of Cl – channels that inhibits cystic 

fibrosis transmembrane regulator ATPase activity. 

Eg5 Inhibitor II 324621 (NSC 83265; S-Trityl-L-cysteine) 

A cell-permeable cysteine thioether compound that potently blocks 

both the basal and microtubule-activated ATPase activities of mitotic 

spindle kinesin Eg5, human (IC = .0 mM and 40 nM, respectively). 

50 

N Eg5 Inhibitor III, Dimethylenastron 324622 [7,7-Dimethyl-4-(3-hydroxyphenyl)-5-oxo-3,4,5,6,7,8hexahydroquinazolin-2(1H)-thione] 

A cell-permeable, potent, specific, and reversible inhibitor of the 

microtubule-stimulated ATPase activity of the mitotic motor, Eg5 

(IC = 200 nM). Exhibits little effect on the ATPase activity of kinesin- 

50 

, -4, -7, and - 0 and is ~ 00-fold more potent than Monastrol (Cat. 

No. 475879). 

N-Ethylmaleimide 34115 (NEM) 

An inhibitor of H + -ATPase that also suppresses the short-circuit current 

(IC = 22 mM) in pancreatic duct cells. 

50 

Folimycin, Streptomyces sp. 344085 (Concanamycin A) 

A highly sensitive and specific inhibitor of vacuolar-type H + -ATPase 

(V-type; K i = 20 pM). 

4-Hydroxynonenal 393204 (HNE; 4-Hydroxy-2-nonenal) 

An irreversible inhibitor of Na + -K + -ATPase activity (IC 50 = 20 mM). 

0 mg $ 7 

00 mg $24 

5 mg $ 46 

5 mg $ 46 

mg $ 5 

mg $95 

5 mg $83 

0 mg $ 2 

500 mg $34 

0 mg $93 

5 mg $52 

g $52 

250 mg $42 

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$232 

5 g $4 

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ATPase Inhibitors, continued 




Hypocrellin B, Hypocrella 

bambusae 

400079 (HC-B) 

A lipid-soluble peryloquinone derivative that causes photo-inactivation 

of Na + -K + -ATPase. 

Mastoparan 444898 (INLKALAALAKKIL) 

Causes a transient Ca 2+ release from the sarcoplasmic reticulum and 

inhibits Na + -K + -ATPase activity (IC 50 = 7.5 mM). 

Mycalolide B, Mycale sp. 475975 A marine toxin that inhibits actin-activated myosin Mg 2+ -ATPase 

activity and also blocks polymerization (IC 50 = 0-50 nM in L 2 0 

leukemia cells). 

NC- 300-B 479915 [2-(2-Dimethylaminobenzylsulfinyl)-5-methoxybenzimidazole] 

A long-acting H + -K + ATPase inhibitor (IC 50 = 4.4 mM at pH 6.0). 

Interested in Studying Mitochondrial Permeability Transition? 

Check out our Inhibitors of Mega Channel and Electron Transport 

www.calbiochem.com/inhibitors 

0 mg $ 69 

mg $ 5 

50 mg $334 

mg $ 00 

Oligomycin 495455 An inhibitor of predominantly F F 0 -type ATPases (IC 50 = 50 mM). 0 mg $66 

Omeprazole 496100 {H 168/68; 5-Methoxy-2[(4-methoxy-3,5-dimethyl-2pyridyl)methylsulfinyl]-1H-benzimidazole} 

An inhibitor of Na + -K + -ATPase activity (IC 50 = 86 mM). 

Acid-degraded omeprazole inhibits Na + -K + -ATPase activity with 

greater potency (IC 50 = 9 mM). 

Ouabain, Octahydrate 4995 (Strophanthin G) 

A cardiotonic steroid that acts as an inhibitor of Na + -K + -ATPase. 

Locks the enzyme in an outward facing manner. 

Phorbol- 2, 3-dibutyrate 524390 (PDBu) 

Stimulates the phosphorylation of Na + -K + ATPase, thereby inhibiting 

its activity. 

Suramin, Sodium Salt 574625 Inhibits Ca 2+ -ATPase in sarcoplasmic reticulum membranes. A 

reversible, competitive inhibitor of protein tyrosine phosphatases. 

Thapsigargin 586005 A cell-permeable tumor-promoting sesquiterpene lactone that 

releases Ca 2+ by inhibiting endoplasmic reticular Ca 2+ -ATPase 

(IC 50 = 4- 3 nM). 

50 mg $89 

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200 mg 

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Inhibitors of Farnesyltransferase (FTase), Geranylgeranyltransferase 

(GGTase), and Methyltransferase 

Prenylation is carried out by cytoplasmic enzymes 

known as geranylgeranyltransferases and 

farnesyltransferases that covalently attach 20-carbon 

(geranylgeranyl) or 15-carbon (farnesyl) isoprenoids to 

the C-terminus of intracellular proteins via thioether 

linkages. Protein farnesyltransferase I (FTase I) and 

protein geranylgeranyltransferase I (GGTase I) recognize 

a CAAX motif as substrate, where C is cysteine, A 

represents any aliphatic amino acid, and X is either 

serine or methionine (FTase I), or leucine (GGTase I). 

The Rab GGTase II attaches geranylgeranyl groups to 

proteins that terminate in either CC or CXC motifs. Many 

proteins in signal transduction pathways are prenylated. 

Perhaps the best-characterized farnesylation products 

are the Ras ATPases. Ras is a guanine nucleotide binding 

protein that transduces growth and differentiation 

signals from receptor tyrosine kinases to the nucleus. 

Mammalian cells express four types of Ras; H-, N-, 

KA-, and KB-Ras. Mutated or oncogenic forms of Ras 

require farnesylation for their ability to transform cells. 

Peptidomimetics designed against the Ras CAAX motif 

have been shown to reverse oncogenic transformation 

by H-Ras and inhibit growth of H-Ras-transformed 

cells. Hence, several types of FTase inhibitors have been 

designed for use as potential anticancer agents. Since 

Ras proteins are posttranslationally modified by FTase 

and carboxymethylation and they act as a common focal 

point for signals from growth factor receptors, use of 

FTase inhibitors is likely to interfere with their action 

and impede cell proliferation. These inhibitors can be 

divided into four groups based on the mechanism of 

their action: (1) competitive inhibitors of farnesyl PPi, (2) 

peptidomimetic inhibitors based on the CAAX motif, (3) 

bisubstrate inhibitors, and (4) inhibitors with unknown 

mechanisms. CAAX peptidomimetics can either 

function as alternative substrates in the FTase catalyzed 

reaction, or they can competitively inhibit FTase without 

serving as substrates. 

References: 

Mazieres, J., et al. 2004. Cancer Lett. 206, 59. 

Sebti, S.M., and Adjei, A.A. 2004. Semin. Oncol. 31 (Suppl ), 28. 

Head, J.E., and Johnston, S.R. 2003. Expert Opin. Emerg. Drugs 8, 63. 

Casey, P.J., and Seabra, M.C. 996. J. Biol. Chem. 271, 5289. 

Lerner, E.C., et al. 995. J. Biol. Chem. 270, 26802. 

Kelloff, G.J., et al. 997. Cancer Epidemiol. Biomarkers Prev. 6, 267. 


N-Acetyl-S-farnesyl-L-cysteine 

(AFC) 

N-Acetyl-S-geranylgeranyl-Lcysteine 

(AGGC) 

More online... www.calbiochem.com/inhibitors/Ftase 

Inhibitors of Farnesyltrasferase (FTase), Geranylgeranyltransferase (GGTase), and Methyltransferase 

110110 (AFC) 

Exhibits high affinity for S-farnesyl-cysteine methyltransferase 

(K m = 20 mM) and thereby inhibits the COOH-terminal methylation 

of proteins in intact cells as well as in cell-free systems. Also inhibits 

fMLP-induced superoxide anion generation (IC 50 = 5 mM). 

110115 (AGGC) 

Exhibits higher affinity (K m = 7 mM) than AFC for carboxyl methyltransferase 

and acts as a more effective inhibitor of fMLP-induced 

superoxide anion generation (IC 50 = 4 mM) than AFC. 

5'-Deoxy-5'-methylthioadenosine 260585 (MeSAdo; MTA) 

Potently inhibits protein carboxymethyltransferase and induces 

apoptosis in leukemia U937 cells. 

FPT Inhibitor I 344150 {(E,E)-2-[(Dihydroxyphosphinyl)methyl]-3-oxo-3-[(3,7,11-trimethyl- 

2,6,10-dodecatrienyl)-amino]propanoic Acid, 3Na} 

A highly selective and potent inhibitor of Ras farnesyl-protein 

transferase (IC 50 = 83 nM). At much higher concentrations, inhibits 

geranylgeranyltransferase I (IC 50 = 26 mM) and II (IC 50 = 47 mM). 

Resistant to cleavage by phosphatases. 

5 mg $92 

5 mg $92 

50 mg $73 

mg $89 

44 Orders Phone 800 854 34 7 


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Inhibitors of Farnesyltrasferase (FTase), Geranylgeranyltransferase (GGTase), and Methyltransferase, continued 


FPT Inhibitor II 344152 {(E,E)-2-[2-Oxo-2-[[(3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy] 

amino]ethyl]phosphonic Acid, 2Na} 

A highly selective and potent inhibitor of Ras farnesyl-protein 

transferase (IC 50 = 75 nM). Also inhibits C 5 and C20 protein 

prenylation in NIH 3T3 cells at higher concentrations. Resistant to 

cleavage by phosphatases. 

FPT Inhibitor III 344154 {(E,E)-[2-Oxo-2-[[(3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy]amino] 

ethyl]phosphonic Acid, (2,2-Dimethyl-1-oxopropoxy)methyl Ester, Na} 

A cell-permeable prodrug ester of farnesyl-protein transferase (FPT) 

inhibitor II that is cleaved to the active FPT inhibitor II by cytosolic 

esterases. Inhibits Ras processing in cells at about 00 mM concentrations. 

Inhibits C 5 and C20 protein prenylation in NIH 3T3 cells. 

FTase Inhibitor I 344510 {N-[2(S)-[2(R)-Amino-3-mercaptopropylamino]-3-methylbutyl]-Phe- 

Met-OH; B581} 

A potent, cell-permeable inhibitor of FTase (IC = 2 nM). Less 

50 

active against GGTase (IC = 790 nM). 

50 

FTase Inhibitor II 344512 (H-Cys-4-Abz-Met-OH) 

A potent FTase inhibitor (IC 50 = 50 nM). 

FTase Inhibitor III 344514 [H-Cys-Val-2-Nal-Met-OH(Nal= 2-naphthylalanine)] 

Potent FTase inhibitor (IC 50 = 50 nM). 

FTI-276 344550 {N-[2-phenyl-4-N[2(R)-amino-3-mercaptopropylamino benzoyl]methionine, 

TFA} 

A highly potent and selective inhibitor of FTase in vitro 

(IC = 500 pM). Less active against GGTase (IC = 50 nM). 

50 50 

FTI-277 344555 {Methyl {N - [2-phenyl-4-N [2(R)-amino-3-mecaptopropylamino] 

benzoyl]}-methionate, TFA} 

Prodrug form of FTI-276 (Cat. No. 344550 ) that acts as a highly 

potent and selective inhibitor of FTase (IC = 50 nM). Inhibits H-Ras 

50 

processing in whole cells (IC = 00 nM), but it does not inhibit 

50 

geranylgeranylated Rap A processing even at 0 mM. Induces accumulation 

of non-farnesylated cytoplasmic H-Ras, which binds to Raf 

protein to form inactive Ras/Raf complexes. FTI-277 is also highly 

effective and selective in disrupting constitutive H-Ras-specific 

activation of MAP kinase. Induces apoptosis in v-K-ras-transformed 

normal rat kidney (KNRK) cells, but not in control NRK cells. 

N FTI-2 48 344557 [2-(((5-((1H-Imidazol-4-ylmethyl)-amino)-methyl)-2'-methylbiphenyl-2-carbonyl)-amino)-4-methylsulfanyl-butyric 

acid, 2TFA] 

Preferentially inhibits protein farnesyltransferase activity 

(IC = 820 pM for mammalian, .8 nM for T. brucei, and 5 nM for 

50 

P. falciparum) compared to protein geranylgeranyltransferase-I 

(IC > .7 mM for mammalian). 

50 

N FTI-2628 344559 [2-(((5-((1H-Imidazol-4-ylmethyl)-amino)-methyl)-2'-methyl-biphenyl- 

2-carbonyl)-amino)-4-methylsulfanyl-butyric acid benzyl ester] 

A cell-permeable benzyl ester prodrug form of FTI-2 48 (Cat. No. 

344557) that preferentially inhibits protein farnesyltransferase 

activity (IC = 530 nM for mammalian and .0 mM for P. falciparum) 

50 

over protein geranylgeranyltransferase-I (IC > 0 mM for mam- 

50 

malian) and displays anti-malarial properties. Potently disrupts Ras 

farnesylation in H-Ras-transformed NIH 3T3 cells (IC = 20 nM) and 

50 

inhibits the growth of P. falciparum in red blood cell (ED = 50 nM). 

50 

GGTI-286 345878 {N-4-[2(R)-Amino-3-mercaptopropyl]amino-2-phenylbenzoyl-(L)leucine 

methyl ester, TFA} 

A cell-permeable form of GGTI-287 (Cat. No. 345880); a very potent 

inhibitor of the processing of the geranylgeranylated Rap A protein 

(IC = 2 mM). 

50 

mg $79 

mg $82 

mg $ 05 

mg $79 

mg $ 0 

250 mg $ 8 

250 mg $ 23 

500 mg $ 9 

500 mg $ 9 

250 mg $ 8 


Phone 800 628 8470 


45


Inhibitors of Farnesyltrasferace (FTase), Geranylgeranyltransferase (GGTase), and Methyltransferase, continued 


GGTI-287 345880 {N-4-[2(R)-Amino-3-mercaptopropyl]amino-2-phenylbenzoyl-(L)leucine,TFA} 

A highly potent and selective GGTase inhibitor in vitro (IC 50 = 5 nM). 

Inhibits FTase only at higher concentrations (IC 50 = 25 nM). 

GGTI-297 345882 {N-4-[2(R)-Amino-3-mercaptopropyl]amino-2-naphthylbenzoyl-(L)leucine, 

TFA} 

A potent and selective GGTase I Inhibitor (IC 50 = 50 nM) relative to 

FTase (IC 50 = 200 nM). 

GGTI-298 345883 {N-4-[2(R)-Amino-3-mercaptopropyl]amino-2-naphthylbenzoyl-(L)- 

Leucine methyl ester, TFA} 

A cell-permeable prodrug form of GGTase I inhibitor, GGTI-297 

(Cat. No. 345882). Inhibits the processing of Rap A (IC 50 = 3 mM) 

but has no effect on the processing of H-Ras even at higher 

concentrations ( 5 mM). 

GGTI-2 33 345884 {4-[[N-(Imidazol-4-yl)methyleneamino]-2-(1-naphthyl)benzoyl]leucine} 

A potent and selective non-thiol inhibitor of GGTase I (IC 50 = 38 nM) 

with a 40-fold selectivity over FTase (IC 50 = 5.4 mM). 

GGTI-2 47 345885 {4-[[N-(Imidazol-4-yl)methyleneamino]-2-(1naphthyl)benzoyl]leucine 

methyl ester} 

Gliotoxin, Gladiocladium 

fimbriatum 

The methyl ester derivative of GGTI-2 33 (Cat No. 345884). 

Selectively inhibits GGTase I over FTase in whole cells. Blocks the 

geranylgeranylation of Rap A with an IC value over 60-fold lower 

50 

than that required to disrupt the farnesylation of H-Ras 

(IC = 500 nM for Rap A versus IC > 30 mM for H-Ras). 

50 50 

371715 {2,3,5a,6-Tetrahydro-6-hydroxy-3(hyroxymethyl)-2-methyl-10H- 

3a,10a-epidithio-pyrazinol[1,2a]indole-1,4-dione} 

An immunosuppressive secondary metabolite produced by several 

pathogenic fungi that specifically inhibits NF-kB activation in B and 

T cells at nanomolar concentrations. 

a-Hydroxyfarnesylphosphonic Acid 390601 (HFPA) 

A potent and selective competitive inhibitor of farnesyl-protein 

transferase (IC = 30 nM). At higher concentrations, it inhibits 

50 

GGTase I (IC = 35.8 mM) and II (IC = 67 mM). Useful for inhibition 

50 50 

of Ras processing in vivo and in vitro. 

L-744,832 422720 {(2S)-2-[[(2S)-2-[(2S,3S)-2-[(2R)-2-Amino-3mercaptopropyl]amino]-3-methylpentyl]oxy]-1-oxo-3phenylpropyl]amino]-4-(methylsulfonyl)-butanoic 

Acid 1-Methylethyl 

Ester; L-744,382} 

A potent and selective thiol-containing peptidomimetic 

farnesyltransferase (FTase) inhibitor with antitumor activities. 

Rapidly blocks p70S6k activation and DNA synthesis, and promotes 

apoptosis in transgenic mice, induces p2 expression and arrests 

cells in G phase. 

Manumycin A, Streptomyces 

parvulus 

Protein Arginine N- 

Methyltransferase Inhibitor, AMI- 

444170 A potent and selective inhibitor of FTase (IC = 5 mM) compared to 

50 

GGTase (IC = 80 mM). 

50 

539209 A cell-permeable, symmetrical sulfonated urea compound that acts 

as a potent, specific and non-AdoMet (S-adenosyl-L-methionine, 

SAM)-competitive inhibitor of protein arginine N-methyltransferases 

(PRMTs; IC = 8.8 mM for PRMT and 3.03 for yeast-RMT p) 

50 

with minimal effect on lysine methyltransferases. Inhibits nuclear 

receptor reporter gene activation in MCF-7 cells, and HIV- RT 

polymerase (IC = 5 mM). 

50 

250 mg $ 5 

250 mg $ 2 

250 mg $ 5 

250 mg $ 46 

250 mg $ 4 

mg $8 

mg $ 42 

5 mg $ 8 

mg $77 

5 mg $95 

46 Orders Phone 800 854 34 7 


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Inhibitors of Glycoprotein Processing and Trafficking 

N- and O-glycan structures contribute significantly 

to biological recognition and cell adhesion during 

immune surveillance, inflammatory reactions, 

hormone action, and viral infections. The cell- and 

tissue-specific changes in cell surface oligosaccharides 

during various phases of development indicate that 

these structures are also involved in cell adhesion and 

migration during embryogenesis. Modifications in the 

branching and extension of N-glycans are also observed 

on cells undergoing oncogenic transformation. These 

modifications may result in alterations in cell adhesion 

and contribute to the invasiveness and metastatic 

potential of malignant cells. 

Inhibitors of Glycoprotein Processing and Trafficking 



Inhibitors of glycoprotein processing act late in the 

N-glycan processing pathway and block the oncogene- 

induced changes in cell surface oligosaccharide 

structures. The various processing inhibitors provide 

useful tools to understand the role of specific kinds 

of oligosaccharide structures in the function of 

various glycoproteins. Because of the specificity of the 

processing inhibitors for individual glycosidases, these 

compounds are also valuable reagents to differentiate 

various enzymatic activities in the cells. 


Australine, Hydrochloride, 

Castanospermum australe 

Benzyl-2-acetamido-2-deoxy-a- 

D-galactopyranoside 

N-(n-Butyl) 

deoxygalactonojirimycin 

N-Butyldeoxynojirimycin, 

Hydrochloride 

Castanospermine, 

Castanospermum australe 

189422 [(1R,2R,3R,7S,7aR)-3-Hydroxymethyl-1,2,7-trihydroxypyrrolizidine] 

Pyrrolizidine alkaloid that inhibits a-glucosidase, amyloglucosidase, 

and glucosidase I. Inhibits glycoprotein processing at the glucosidase 

I step, resulting in the accumulation of glycoproteins containing 

Glc 3 Man 79 (GlcNAc)2-oligosaccharides. Does not inhibit a- or bgalactosidase, 

b-glucosidase, or a- or b-mannosidase. 

200100 (Benzyl-a-GalNAc) 

Used as an inhibitor of O-linked glycosylation in a variety of cell lines. 

It has also been used to inhibit 2,3(O)-sialyltransferase and disrupt 

glycoprotein targeting in HT-29 cells. Substrate for N-acetyl-b-Dglucosaminyltransferase. 

mg $87 

00 mg $ 5 

203994 A potent and selective inhibitor of a-D-galactosidase. 5 mg $ 68 

203996 (N-Butyl-DNJ, HCl; NB-DNJ, HCl) 

A non-hormonal, alkylated iminosugar that acts as a transition state 

analog inhibitor of ceramide-specific glycosyltransferases and ER 

a-glucosidases I and II. Displays a broad-spectrum antiviral activity 

by aiding the misfolding of glycoproteins. 

218775 (1S,6S,7R,8aR)-Tetrahydroxyoctahydroindolizine 

Plant alkaloid inhibitor of several b-glucosidases and a-glucosidases, 

including those involved in N-linked processing of glycoproteins. 

Resulting oligosaccharides are primarily Glu 3 Man 7-9 (GlcNAc) 2 . 

Reduces bFGF induced angiogenesis in mice. Inhibits endothelial cell 

migration and invasion of basement membrane. Exhibits anti-viral 

properties. Typically used at – 0 µg/ml. 

Conduritol B Epoxide 234599 An irreversible, potent, and specific inhibitor of glucocerebrosidase in 

cultured neurons. Has also been shown to inhibit a-glucosidase from 

yeast and rabbit intestinal sucrase-isomaltase complex. 

2-Deoxy-D-galactose 259580 Suggested to act as an inhibitor of fucosylation. It has also been used 

for competitive elution of Anadarin P lectin (a galactosyl-binding 

lectin from blood clam). 

Deoxyfuconojirimycin, 

Hydrochloride 

Deoxygalactonojirimycin, 

Hydrochloride 

More online... www.calbiochem.com/inhibitors/glycoprotein 

259541 (DFJ; 1,5-Dideoxy-1,5-imino-L-fucitol, HCl) 

Potent and specific competitive inhibitor (K = 0 nM) of human liver 

i 

a-fucosidase. 

259544 (DGJ; 1,5-Dideoxy-1,5-imino-D-galactitol; Galactostatin, HCl) 

A potent and selective a-galactosidase inhibitor. 

0 mg $20 

mg $38 

00 mg $2 3 

g $87 

5 mg $ 30 

5 mg $ 59 


Phone 800 628 8470 


47


Inhibitors of Glycoprotein Processing and Trafficking, continued 


-Deoxymannojirimycin, 

Hydrochloride 

-Deoxynojirimycin, Hydrochloride 260684 (DNJ, HCl) 

Kifunensine, Kitasatosporia 

kifunense 

260575 (1,5-Dideoxy-1,5-imino-D-mannitol, HCl; DMJ) 

Special a-mannosidase I inhibitor that blocks conversion of high 

mannose to complex oligosaccharides. 

Specific glucosidase inhibitor, including trimming glucosidases I 

and II, that sequentially removes the three glucose residues from 

precursor Glc 3 Man 9 GlcNAc 2 in N-linked glycan biosynthesis. 

422500 A potent alkaloid inhibitor of mannosidase I. An ineffective inhibitor 

of mannosidase II and the endoplasmic reticulum a-mannosidase. 

Mannostatin A, Hydrochloride 444042 A potent glycosidase inhibitor that blocks mannosidase II processing 

in the Golgi more effectively than Swainsonine (Cat. No. 574775). 

DL-threo-PDMP, Hydrochloride 513100 (1-Phenyl-2-decanoylamino-3-morpholino-1-propanol, HCl) 

PDMP closely resembles the natural sphingolipid substrate of brain 

glucosyltransferase and is a potent and competitive inhibitor of this 

enzyme. 

Swainsonine, Swainsona canescens 574775 [8ab-Indolizidine-1a,2a,8b-triol; (1S,2S,8R,8aR)-Trihydroxyindolizidine] 

Reversible active-site inhibitor of lysosomal a-mannosidase. Blocks 

the processing of high mannose to complex type oligosaccharides. 

Tunicamycin, Streptomyces 

lysosuperficus 

654380 A nucleoside antibiotic that inhibits N-linked glycosylation and 

blocks the formation of N-glycosidic protein-carbohydrate linkages. 

A dedicated 

resource for 

glycobiology- 

related kits, 

enzymes, 

antibiotics, 

substrates, and 

carbohydrateprotein 

interaction 

tools. 

5 mg $ 03 

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mg 

0 mg 

$39 

$ 76 

mg $20 

mg $244 

50 mg $ 39 

500 mg $62 

0 mg 

50 mg 

$ 06 

$3 3

Heat Shock Protein Inhibitors 

Heat shock proteins (HSPs) are a group of proteins that 

are expressed at higher levels when cells are exposed 

to higher temperatures. The upregulation of the HSPs 

is a key part of the heat shock response. Production of 

high levels of heat shock proteins can also be triggered 

by exposure to different kinds of environmental 

stress conditions, such as infection, inflammation, 

exposure of the cell to toxins. Depending on the level 

of stress, injured cells may undergo either necrosis 

or apoptosis. Under extreme stress conditions, when 

there is diminution in regulated activation of apoptotic 

pathways, cells undergo necrosis. At lower stress levels, 

cells activate their apoptotic machinery. However, at 

sub-lethal stress levels, cells may attempt to survive 

and activate a stress response system that includes a 

rapid induction of HSPs. HSPs interact with diverse 

protein substrates and assist in their folding and in the 

elimination of any misfolded or damaged molecules. 

They are transiently expressed during cell cycle to 




7-AAG 100068 An inhibitor of Hsp90. 500 mg $ 78 

7-DMAG 100069 A potent antitumor analog of 7-AAG (Cat. No. 00068) that binds 

to the ATPase site of human Hsp90a with high affinity (GI 50 = 5 nM 

for 7-DMAG vs. 20 nM for 7-AAG in the NCI 60-cell panel in vitro 

activity screen), and displays excellent bioavailability and aqueous 

solubility. 

Geldanamycin, Streptomyces 

hygroscopicus 

500 mg $ 78 

345805 A specific inhibitor of Hsp90. 00 mg $ 80 

Heat Shock Protein Inhibitor I 373260 A benzylidene lactam compound that blocks the induction of heat 

shock proteins Hsp70, Hsp72, and Hsp 05. 

Heat Shock Protein Inhibitor II 373265 A metabolite of the Heat Shock Protein Inhibitor I (Cat. No. 373260) 

that exhibits similar in vitro activity. 

Hsp25 Kinase Inhibitor 385880 A 3-residue peptide that acts as a potent and selective inhibitor of 

mammalian heat-shock protein (Hsp25) kinase [also called mitogenactivated 

protein kinase-activated protein kinase-2 (MAPKAP 

kinase-2)]. Inhibition is competitive with respect to the substrate 

peptide (K = 8. µM) and non-competitive with respect to ATP (K = 

i i 

34 µM). 


Hsp27 ELISA Kit 

Kit Contents: Anti-Hsp27 coated microplate, Hsp27 standard, lysis 

buffer, assay diluent, detector antibody, wash buffer, HRP-conjugate, 

TMB, stop solution, and a user protocol. kit = 96 tests. 


prevent differentiating cells from undergoing apoptosis. 

Many tumor cells have constitutively elevated levels 

of HSP that impart protection against cytotoxic agents 

thereby raising the apoptosis threshold of these cells. 

This abnormal expression of HSPs may lead to multidrug 

resistance in aggressively growing tumors. Many 

HSPs, including HSP27 and HSP70, have been shown 

to block apoptosis. HSPs can also allow cancerous 

cells to escape the immunosurveillance mediated by 

death ligands and can render these cells resistant to 

chemotherapy. Hence, HSPs are fast becoming new 

targets for therapeutic interventions. 

References 

Chiosis, G., et al. 2004. Drug Discov. Today 9, 88 . 

Odunuga, O.O., et al. 2004. Bioessays 26, 058. 

Creagh, E.M., et al. 2000. Leukemia 14, 6 . 

Jolly,C., and Morimoto, R.I. 2000. J. Natl. Cancer Inst. 92, 564. 

Gibbons, N.B., et al. 2000. Prostate 45, 58. 

Arrigo, A.P. 2000. Pathol. Biol. (Paris) 48, 280. 

5 mg $ 07 

0 mg $ 23 

mg $90 

Find more than 20 anti-Hsp antibodies at our updated Antibody Resource 

www.calbiochem.com/antibody resource 


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49


Inhibitors of Mitochondrial Function 

In addition to being the energy generators in the cell, 

mitochondria play an important role in cell survival and 

cell death. In fact, any abnormality in the mitochondrial 

energy generation machinery can lead to cell death. 

Mitochondria are highly vulnerable to inhibition or 

uncoupling of the energy harnessing process and their 

structural and functional characteristics provide a 

number of primary targets for xenobiotic-induced 

bioenergetic failure. Inhibitors of mitochondrial function 

include compounds that act as electron transport 

inhibitors, uncouplers of oxidative phosphorylation, 

respiratory chain inhibitors, phosphorylation inhibitors, 

ionophores, and Krebs cycle inhibitors. The study of 

mitochondrial metabolism using these compounds has 

led to the identification of bioenergetic control points 

for cell replication, cell differentiation, and cell death. 

Use of specific inhibitors has also helped to distinguish 

the electron transport system from the phosphorylation 

system and define the sequence of redox carriers along 

the respiratory chain. Five different enzyme complexes 

have been recognized in the mitochondria. Complexes 

I, II, III, and IV are the electron transfer complexes, 

whereas complex V is an energy-conserving complex. It 

catalyzes ATP-P i exchange and ATP hydrolysis. 

Electron transport inhibitors act by preventing the 

passage of electrons from one carrier to the next. 

Irreversible inhibitors may cause a complete stoppage of 

respiration, whereas competitive inhibitors may allow 

some oxygen consumption and passage of electrons, 

but the conditions are not optimum to maintain a 

chemiosmotic gradient. Hence, the addition of ADP 

does not affect respiration. Electron transport system 

(ETS) accepts energy from carriers in the mitochondrial 

matrix and stores it to a form that can be used to 

phosphorylate ADP. NAD and FAD are the two energy 

carriers that donate energy to ETS. NAD carries energy 

to complex I (NADH-Coenzyme Q reductase) of the 

electron transport chain, whereas FAD is a part of the 

succinate dehydrogenase complex (complex II). 

Uncouplers of oxidative phosphorylation, such as 

CCCP and 2,4-dintirophenol, inhibit mitochondrial 

function by abolishing the obligatory linkage between 

the respiratory chain and the phosphorylation system 

in intact mitochondria. Here the electron transport 

system is uninhibited due to complete and irreversible 

dissipation of the chemiosmotic gradient. 

 

 

 

50 Orders Phone 800 854 34 7 


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2e- 

 

 

 

 

 

 

2e - 

 

2e- 

 

2e- 

2e-

Inhibitors of Mitochondrial Function 




Atractyloside, Dipotassium Salt, 

Atractylis gummifera 

Bongkrekic Acid, 

Triammonium Salt 

Carbonyl Cyanide 

m-Chlorophenylhydrazone 

Carboxyatractyloside, 

Atractylis gummifera 

189300 (ATR, 2K) 

Toxic compound originally isolated from the Mediterranean 

thistle Atractylis gummifera. Acts as an ADP/ATP translocase 

(AAT) inhibitor. Also causes the release of cytochrome c from 

mitochondria. 

203671 (BA, 3NH4; 3-Carboxymethyl-17-methoxy-6,18,21-trimethyldocosa- 

2,4,8,12,18,20-heptaenedioic Acid) 

Acts as a ligand of the adenine nucleotide translocator. A potent 

inhibitor of mitochondrial megachannel (permeability transition 

pore). Significantly reduces signs of apoptosis induced by nitric 

oxide. Prevents the apoptotic breakdown of the inner mitochondrial 

transmembrane potential (∆y m ), as well as a number of other 

phenomena linked to apoptosis. 

215911 (CCCP) 

Protonophore. Uncoupling agent for oxidative phosphorylation that 

inhibits mitochondrial function. Approximately 00 times more 

effective than 2,4-dinitrophenol. Binds with cytochrome c oxidase 

with high affinity (K d = 270 nM). Inhibits transport processes and 

depresses growth. 

216200 (C-ATR; CAT) 

Toxic compound originally isolated from the Mediterranean thistle 

Atractylis gummifera. A highly selective inhibitor of the cytosolic 

side-specific mitochondrial ADP/ATP carrier (AAC; K i < 0 nM). 

CGP-37 57 220005 [7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one] 

A cell-permeable benzothiazepine derivative of clonazepam that 

acts as a specific and potent inhibitor of the mitochondrial Na + / 

Ca2+ exchanger (IC = 360 nM). Enhances the export of Ca 50 2+ from 

isolated mitochondria. Also reported to directly inhibit voltagegated 

Ca2+ channels. 

N (-)-Deguelin, Mundulea sericea 252740 A cell-permeable rotenoid compound that potently inhibits 

mitochondrial bioenergetics (IC =6.9 nM for NADH:ubiquinone 

50 

oxidoreductase activity in bovine heart ETP; IC = nM for phorbol 

50 

ester induced ornithine decarboxylase activity in MCF-7 cells) 

and induces apoptosis and cell cycle arrest. Selectively blocks Akt 

activation with minimal effects on MAPK signaling. Also shown to 

activate AMPK activity and inhibit COX-2 expression. 

F 6 341246 A cell-permeable, fluorogenic, delocalized lipophilic cationic 

compound that acts as a mitochondrial toxin and possesses the dual 

ability to induce apoptosis as well as necrosis in tumor cells. Preferentially 

accumulates in mitochondria, inhibits oxidative phosphorylation 

and causes mitochondrial transmembrane depolarization. The 

incorporation and localization of F 6 can be easily monitored by its 

fluorescence property. 

Hexokinase II VDAC Binding 

Domain Peptide, Cell-Permeable 

376816 (H-RQIKIWFQNRRMKWKK-MIASHLLAYFFTELN-NH 2 ; HXK2VBD-cpm) 

A cell-permeable peptide analog of Hexokinase II VDAC binding 

domain peptide. The internalization domain of the Antennapedia 

homeoprotein is fused to the methionine amino terminal. Shown to 

completely detach and translocate HXK2 from mitochondria to the 

cytosol in HeLa cells at 00 mM. Does not induce Bax translocation 

or cytochrome c release when used alone. However, it markedly 

sensitizes cells to cytochrome c release and to the induction 

of apoptosis when used in combination with a Bax-dependent 

apoptosis inducer, Indomethacin (Cat. No. 405268). 

Oligomycin 495455 A mixture of A, B, and C isomers. A macrolide antibiotic that inhibits 

membrane-bound mitochondrial ATPase (F ), preventing phosphoryl 

group transfer. Induces apoptosis in cultured human lymphoblastoid 

and other mammalian cells. 

Rotenone 557368 A mitochondrial toxin and a potent, reversible, and competitive 

inhibitor of complex I (NADH-CoQ reductase) of the respiratory 

chain. Also inhibits cellular proliferation in mouse liver. 

50 mg $83 

500 mg $265 

250 mg $7 

5 mg $207 

5 mg $ 8 

5 mg $67 

25 mg $ 42 

mg $ 90 

0 mg $66 

g $64 


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5


Inhibitors of Mitochondrial Function, continued 


Ru360 557440 [(m)[(HCO 2 )(NH 3 )4Ru] 2 OCl 3 ] 

A cell-permeable oxygen-bridged dinuclear ruthenium amine 

complex that has been shown to bind to mitochondria with 

high affinity (K d = 340 pM). Specifically blocks Ca 2+ uptake into 

mitochondria in vitro (IC 50 = 84 pM) and in situ in intact myocytes 

(complete block after incubation with ~ 0 mM of Ru360 for 30 min). 

Does not affect other cellular Ca 2+ transport processes involved in 

cardiac muscle contraction, even at micromolar levels. 

( set = 0 × 0 mg) 

SFK 565833 (Suppressor of FK-506 1) 

A cell-permeable amidine compound that has been shown to interact 

with Por p (YVDAC ), a channel protein in the outer mitochondrial 

membrane, and to modulate ionic balance in Saccharomyces 

cerevisiae. It suppresses the ability of FK-506 to inhibit yeast growth 

in high NaCl-containing media (IC 50 ~ .5–2.5 mM), while in low 

NaCl-containing media, it causes mitochondrially-induced death by 

stimulating the release of reactive oxygen species (ROS). 

Valinomycin, Streptomyces 

fulvissimus 

Mitochondrial Permeability Transition 

Pore Reagents Set 

Contains g of Adenosine 5'-Diphosphate, Potassium Salt 

(Cat. No. 7 05), 500 mg of Bongkrekic Acid, Triammonium Salt 

(Cat. No. 20367 ), 5 mg of Carboxyatractyloside, Atractylis gummifera 

(Cat. No. 2 6200), and 00 mg of Cyclosporin A, Tolypocladium 

inflatum (Cat. No. 239835). 

Cat. No. 475876 1 set $325 

676377 A cyclododecadepsi-peptide ionophore antibiotic. Potassium 

ionophore of the mobile ion-carrier type that transports alkali 

metal ions across artificial or biological lipid membranes. Induces 

K + conductivity in cell membranes at concentrations as low as 

0 -8 M. Often used in membrane electrode systems for determining 

K + concentration. Uncouples oxidative phosphorylation by binding to 

sites on membranes rich in sulfhydryl groups. Induces apoptosis in 

murine thymocytes. Also reported to inhibit NGF-induced neuronal 

differentiation. 

52 Orders Phone 800 854 34 7 


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500 mg 

mg 

set 

$ 46 

$255 

$352 

0 mg $ 26 

25 mg 

00 mg 

$65 

$225

NF-kB Activation Inhibitors 

NF-kB, a eukaryotic transcription factor plays an 

important role in inflammation, autoimmune response, 

cell proliferation, and apoptosis by regulating the 

expression of genes involved in these processes. It 

consists of homo- or heterodimers of different subunits, 

which belong to a family of Rel/NF-kB proteins. Five 

different Rel proteins [p50, p52, p65 (Rel A), RelB, and 

c-Rel] have been identified thus far. The most prevalent 

activated form of NF-kB is a heterodimer of p50 or 

p52 subunit and p65, which contains transactivation 

domains necessary for gene induction. In unstimulated 

cells, NF-kB is sequestered in the cytoplasm in an 

inactive form, bound to regulatory proteins called 

inhibitors of kB (IkB), of which IkBa and IkBb are 

considered to be the most important. IkBa is associated 

with transient NF-kB activation, whereas IkBb is 

involved in sustained activation. 

The activity of NF-kB is tightly regulated by interaction 

with inhibitory IkB proteins. In most resting cells, NFkB 

is sequestered in the cytoplasm in an inactive form 

associated with inhibitory molecules, such as IkBa, 

IkBb, IkBh, p105, and p100. This interaction blocks the 

ability of NF-kB to bind to DNA and results in the NF-kB 

complex being primarily localized to the cytoplasm due 

to a strong nuclear export signal in IkBa. 

Stimulation of cells by inflammatory cytokines, UV 

light, or reactive oxygen species leads to the rapid 

phosphorylation, ubiquitination, and ultimately 



proteolytic degradation of IkB, which frees NF-kB from 

the NF-kB-IkB complex. NF-kB then translocates to the 

nucleus where it binds to kB enhancer elements of proinflammatory 

target genes to induce transcription. NFkB 

is highly activated at sites of inflammation in diverse 

diseases and induces transcription of pro-inflammatory 

cytokines, chemokines, adhesion molecules, MMPs, 

COX-2, and inducible nitric oxide (iNOS). Hence, NF-kB 

has been considered as a desirable target for therapy in 

various inflammatory diseases. In most cancer cells, 

NF-kB is constitutively active and resides in the nucleus. 

In some cases, this may be due to chronic stimulation 

of the IKK pathway, while in others the gene encoding 

IkBa may be defective. Such continuous nuclear NF-kB 

activity not only protects cancer cells from apoptotic 

cell death, but may even enhance their growth activity. 

Designing antitumor agents to block NF-kB activity or 

to increase sensitivity to conventional chemotherapy 

may have great therapeutic value. 

References: 

Pande, V., and Ramos, M. J. 2005. Curr. Med. Chem. 12, 357. 

Bouwnecster, T. et al. 2004. Nat. Cell Biol. 6, 97. 

Marienfeld, R., et al. 2003. J. Biol. Chem. 278, 9852. 

Ghosh, S., and Karin M. 2002. Cell 109, S8 . 

Delhase, M., et al. 999. Science 284, 309. 

Rahman, A., et al. 999. J. Immunol. 162, 5466. 

Miyazawa, K., et al. 998. Am. J. Pathol. 152, 793. 

Zandi, E., et al. 998. Science 281, 360. 

Stancovski, I., and Baltimore, D. 997. Cell 91, 299. 

Baldwin, A.S. Jr. 996. Annu. Rev. Immunol. 14, 649. 

More online... www.calbiochem.com/inhibitors/NFKB 


Phone 800 628 8470 


53


NF-kB Activation Inhibitors 


BAY -7082 196870 {(E)3-[(4-Methylphenyl)sulfonyl]-2-propenenitrile} 

Potential anti-inflammatory agent that selectively and irreversibly 

inhibits the TNFa-inducible phosphorylation of IkBa (IC 50 = 0 mM) 

without affecting the constitutive IkBa phosphorylation. Decreases 

nuclear translocation of NF-kB and inhibits TNFa-induced surface 

expression of the endothelial-leukocyte cell adhesion molecules 

E-selectin, VCAM- , and ICAM- . 

N InSolution BAY -7082 196871 A 00 mM ( 0 mg/483 ml) solution of BAY -7082 


BAY -7085 196872 {(E)3-[(4-t-Butylphenyl)sulfonyl]-2-propenenitrile} 

Exhibits biological properties similar to that of BAY -7082 

(Cat. No. 96870). BAY -7085 has also been shown to have potent 

anti-inflammatory properties in vivo. 

CAPE 211200 (Caffeic Acid Phenethyl Ester, Synthetic) 

An active component of propolis from honeybee hives with antiviral, 

anti-inflammatory, and immunomodulatory properties. Has been 

shown to act as a potent and specific inhibitor of NF-kB activation. 

(E)-Capsaicin 211274 {[(E)-N-(4-Hydroxy-3-methoxyphenyl)methyl]-8-methyl-6nonenamide} 

An active constituent of cayenne pepper that has anti-nociceptive 

and anti-inflammatory effects. Inhibits NF-kB activation by TNF-a. 

N Evodiamine, Evodia rutaecarpa 341211 A cell-permeable quinazolinocarboline that suppresses both 

inducible and constitutive NF-kB activation and 

NF-kB-regulated gene expression by inhibiting IKK activation. 

Gliotoxin, Gladiocladium 

fimbriatum 

Helenalin, A. chamissonis ssp. 

foliosa 

371715 {2,3,5a,6-Tetrahydro-6-hydroxy-3(hyroxymethyl)-2-methyl-10H- 

3a,10a-epidithio-pyrazinol[1,2a]indole-1,4-dione} 

An immunosuppressive secondary metabolite produced by several 

pathogenic fungi that specifically inhibits NF-kB activation in B and 

T cells at nanomolar concentrations. 

374000 A cell-permeable pseudoguainolide sesquiterpenoid lactone that 

inhibits NF-kB-DNA binding activity by selectively alkylating the p65 

subunit of NF-kB. Does not inhibit IkB degradation or NF-kB nuclear 

translocation. 

Hypoestoxide, Hypoestes rosea 401006 A naturally occurring, cell-permeable diterpene with antiinflammatory 

properties. Acts as a selective and direct inhibitor of 

IkB kinase (IC 50 = 24 mM) in TNF-a stimulated HeLa cells thereby 

prevents NF-kB activation. 

IkB Kinase Inhibitor Peptide, 


IkB Kinase Inactive Control 

Peptide, Cell-Permeable 

401477 (Ac-AAVALLPAVLLALLAPDDRHDSGLDSMKDE-NH 2 ) 

A 4-amino acid peptide corresponding to the active IkB 

phosphorylation recognition sequence, linked to the hydrophobic 

region of the fibroblast growth factor signal peptide to aid in cellular 

delivery. Specifically inhibits LPS-induced IkB degradation by IkB 

kinases (IKK) in RAW 264.7 cells ( 0 mM) or TNF-a production 

(IC 50 > 0 mM). 

401478 (Ac-AAVALLPAVLLALLAPDDRHDAGLDAMKDE-NH 2 ) 

An inactive control for IkB Kinase Inhibitor Peptide (Cat. No. 

40 477). Corresponds to the mutated recognition sequence of IkB 

(Ser 32 → Ala and Ser 36 → Ala), linked to the hydrophobic region of 

the fibroblast growth factor signal peptide to aid in cellular delivery. 

Does not have any inhibitory effect on LPS-induced IkB degradation 

by IkB kinases (IKK) in RAW 264.7 cells at 50 mg/ml. 

IKK Inhibitor II, Wedelolactone 401474 (7-Methoxy-5,11,12-trihydroxy-coumestan; Wedelolactone, Eclipta alba) 

The naturally isolated active ingredient of the herbal medicine, 

Eclipta alba, that acts as a selective and irreversible inhibitor of IKKa 

and b kinase activity (IC 50 < 0 mM). Inhibits NF-kB-mediated gene 

transcription in cells by blocking the phosphorylation and degradation 

of IkB. 

0 mg $68 

0 mg $68 

0 mg $88 

25 mg $ 00 

00 mg $62 

5 mg $ 49 

mg $8 

500 mg $ 35 

mg $ 50 

mg $ 90 

54 Orders Phone 800 854 34 7 


Fax 800 776 0999 


mg 

mg 

$ 95 

$79

NF-kB Activation Inhibitors, continued 




N IKK Inhibitor III, BMS-34554 401480 {4-(2´-Aminoethyl)amino-1,8-dimethylimidazo[1,2-a]quinoxaline, HCl} 

A cell-permeable, potent, selective, and allosteric site-binding 

inhibitor of IKK-2 (IC 50 ~300 nM). Exhibits ~ 0 fold greater 

selectivity over IKK- (IC 50 ~4 mM). 

IKK-2 Inhibitor, SC-5 4 401479 (SC-514) 

A cell-permeable, potent, reversible, ATP-competitive, and highly 

selective inhibitor of IKK-2 (IC 50 ~3- 2 mM for IKK-2 homodimer, 

IKK- /IKK-2 heterodimer, and IKK-2). Shown to specifically block 

NF-kB-dependent gene expression, but not MAP kinase pathways, 

in stimulated RASF synovial fibroblast cells. Does not inhibit the 

phosphorylation and activation of the IKK complex. 

N InSolution IKK-2 Inhibitor, SC-5 4 401485 A 25 mM ( mg/ 78 ml) solution of IKK-2 Inhibitor, 

SC-5 4 (Cat. No. 40 479) in DMSO. 

IKK-2 Inhibitor IV 401481 {[5-(p-Fluorophenyl)-2-ureido]thiophene-3-carboxamide} 

A cell-permeable, potent, and selective inhibitor of IKK-2 

(IC 50 = 8 nM) with selectivity over IKK- , JNK, and p38 MAPK. 

N IKK-2 Inhibitor V 401482 [N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide; 

IMD-0354] 

A cell-permeable salicylamide compound that acts as an IKK-2 

inhibitor by selectively blocking IkBa phosphorylation 

(IC 50 ~250 nM) and thereby prevents the induction of NF-kB p65 

nuclear translocation. 

N IKK-2 Inhibitor VI 401483 [(5-Phenyl-2-ureido)thiophene-3-carboxamide] 

An ureido-thiophenecarboxamide compound that acts as a potent 

inhibitor of IKK-2 (IC 50 = 3 nM). 

Isohelenin, Inula sp. 416157 (Isoalantolactone) 

A cell-permeable sesquiterpene lactone with anti-inflammatory 

properties. Acts as a highly specific, potent, and irreversible inhibitor 

of NF-kB activation by preventing IkBa degradation. Does not 

affect the DNA binding activity of activated NF-kB or inhibit Fyn 

and Src kinase activities. 

NEMO-Binding Domain Binding 

Peptide, Cell-Permeable 

NEMO-Binding Domain Binding 

Peptide, Cell-Permeable, Negative 

Control 

480025 (DRQIKIWFQNRRMKWKKTALDWSWLQTE; NBD-Binding Peptide, 

Cell-Permeable) 

A cell-permeable Antennapedia-NBD (NEMO binding domain) (wild 

type) fusion peptide that exhibits anti-inflammatory activity in 

mouse model of acute inflammation. NBD is an amino-terminal 

a-helical region of the NEMO (NF-kB essential modifier; IKKg) 

associated with a carboxyl-terminal segment of IKKa and IKKb. 

Blocks the association of NEMO with the IKK complex and prevents 

NF-kB activation. 

480030 (DRQIKIWFQNRRMKWKK-TALDASALQTE; NBD-Binding Peptide, 

Cell-Permeable, Negative Control) 

A cell-permeable, Antennapedia-NBD mutated (Trp 739 → Ala and 

Trp 74 → Ala) fusion peptide analog of NEMO-Binding Domain Binding 

Peptide (Cat. No. 480025) that serves as a negative control. 

Reported to be defective in binding to NEMO. 

NF-kB Activation Inhibitor 481406 [6-Amino-4-(4-phenoxyphenylethylamino)quinazoline] 

A cell-permeable quinazoline compound that acts as a potent inhibitor 

of NF-kB transcriptional activation (IC 50 = nM in Jurkat cells) and 

LPS-induced TNF-a production (IC 50 = 7 nM in murine splenocytes). 

Does not exhibit cellular toxicity at concentrations required for 

inhibition of NF-kB transcriptional activation (IC 50 > 0 mM) or TNF-a 

production (IC 50 > 0 mM). 

N InSolution NF-kB Activation 


481407 A 0 mM ( mg/28 ml) solution of NF-kB Activation Inhibitor (Cat. 

No. 48 406) in DMSO. 

mg $ 58 

mg $79 

mg $79 

500 mg $84 

5 mg $ 63 

mg $ 2 

mg 

500 mg 

500 mg 

mg 

mg 

$ 84 

$ 64 

$ 64 

$79 

$79 


Phone 800 628 8470 


55


NF-kB Activation Inhibitors, continued 


N NF-kB Activation Inhibitor II, 

JSH-23 

NF-kB SN50, Cell-Permeable 

Inhibitor Peptide 

NF-kB SN50M, Cell-Permeable 

Inactive Control Peptide 

481408 (4-Methyl-N 1 -(3-phenylpropyl)benzene-1,2-diamine) 

A cell-permeable diamino compound that selectively blocks 

nuclear translocation of NF-kB p65 and its transcription activity 

(IC 50 = 7. mM in a NF-kB reporter assay using RAW 264.7) without 

affecting IkB degradation. Shown to suppress DNA-binding of 

NF-kB and downregulate LPS-induced gene expression and 

apoptotic chromatin condensation. 

481480 (AAVALLPAVLLALLAPVQRKRQKLMP) 

Contains the nuclear localization sequence (NLS) of the transcription 

factor NF-kB p50 linked to the hydrophobic region (h-region) of the 

signal peptide of Kaposi fibroblast growth factor (K-FGF). The peptide 

N-terminal K-FGF h-region confers cell-permeability, while the NLS 

(360-369) inhibits translocation of the NF-kB active complex into 

the nucleus. 

481486 An inactive control for SN50 peptide (Cat. No. 48 480). Corresponds 

to the SN50 peptide sequence with substitutions of Lys 363 for Asn and 

Arg 364 for Gly in the NLS region. 

N Oridonin, R. rubescens 496915 A cell-permeable diterpenoid compound with anti NF-kB activity. 

Shown to block LPS-induced NF-kB activity in Jurkat and in RAW 

264.7 murine macrophages, and inhibit NF-kB transcriptional 

activity (IC 50 ~5 mg/ml in MT- cells) by disrupting NF-kB DNAbinding 

activity without interfering with its nuclear translocation. 

Parthenolide, Tanacetum 

parthenium 

512732 A sesquiterpene lactone with anti-inflammatory, antisecretory, and 

spasmolytic properties. Inhibits NF-kB and activation of MAP kinase. 

PPM- 8 529570 (2-Benzoylamino-1,4-naphthoquinone) 

A novel, cell-permeable, anti-inflammatory agent that inhibits the 

expression of inducible nitric oxide synthase (iNOS; IC 50 ~5 mM). Acts 

by blocking the activation of NF-kB in vitro and in vivo. 

Sulfasalazine 573500 {5-[4-(2-Pyridylsulfamoyl)phenylazo]salicylic Acid; SSZ} 

A cell-permeable, anti-inflammatory agent that acts as an inhibitor 

of glutathione S-transferase (IC 50 = 0 mM in H-69 cell line). Prevents 

NF-kB activation and induces apoptosis in T lymphocytes. 

TIRAP Inhibitor Peptide, 


TIRAP Inhibitor Peptide, Control, 


613570 [Ant-Tirap 138-151 ; Mal Peptide; MyD88-Adapter-Like Peptide; TIRAP 

Peptide; Toll-interleukin 1 Receptor (TIR) domain-containing Adapter 

Protein Peptide] 

A cell-permeable, synthetic peptide corresponding to mouse tollinterleukin 

receptor (TIR) domain-containing adapter protein 

38– 5 (TIRAP) fused to the Drosophila Antennapedia sequence. 

Specifically inhibits LPS-induced, but not CpG-induced, NF-kB 

activation, PKR phosphorylation, and JNK phosphorylation in RAW.kB 

cells at ~40 mM. Also reported to block IkBa degradation. 

613571 [Ant-Tirap 151-138 ; Mal Peptide; MyD88-Adapter Like Peptide; TIRAP 

Peptide, Control; Toll-interleukin 1 Receptor (TIR) domain-containing 

Adapter Protein Peptide] 

A cell-permeable, synthetic peptide containing mouse tollinterleukin 

receptor (TIR) domain-containing adapter protein 5 – 

38 reverse sequence (TIRAP) fused to the Drosophila Antennapedia 

sequence. Serves as a control for TIRAP Inhibitor Peptide (Cat. No. 

6 3570). 

5 mg $ 8 

500 mg $ 57 

500 mg $ 57 

5 mg $82 

50 mg $62 

0 mg $98 

00 mg $33 

mg $207 

mg $207 

56 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Phosphodiesterase (PDE) Inhibitors 

cAMP and cGMP, two important second messengers 

molecules are hydrolyzed by phosphodiesterases (PDEs) 

in the cell, leading to cessation of cAMP and cGMPdependent 

effects. PDEs comprise a large group of 

enzymes organized into 11 distinct families based on 

their biochemical and molecular properties. Many of 

these isozymes are differently expressed and regulated 

in different cells and exhibit distinct selectivity for 

cAMP and cGMP. 

PDEs contain three functional domains: a regulatory Nterminus, 

a central catalytic domain, and a regulatory Cterminus. 

All isozymes exhibit significant homology in 

their catalytic domain. The N- and C-terminal domains 

also display moderate homology within families and 

impart specific characteristics to different subtypes. 

The N-terminus is involved in allosteric regulation and 

membrane targeting. The C-terminus is believed to be 

involved in dimerization and possess docking sites for 

PDE-specific kinases. 

Due to their involvement in inflammation, asthma, and 

cardiovascular complications, PDEs are considered to 

be attractive targets for pharmacological intervention. 

A number of PDE inhibitors have been developed that 

target specific isoenzymes, thereby increasing tissue 

selectivity and minimizing any side effects. 

Phosphodiesterase Inhibitors 




Calmidazolium Chloride 208665 (Compound R 24571) 

A cell-permeable analog of sepazonium that is at least 50 times 

more potent than Trifluoperazine (Cat. No. 642 50) as an inhibitor of 

brain PDE I (IC 50 = 0 nM). 

Chlorpromazine, Hydrochloride 215921 {2-Chloro-10-[3´-(dimethylamino)propyl]phenothiazine, HCl} 

An inhibitor of PDE I (IC 50 = 7 mM). Acts as a peripheral vasodilator. 

Cilostamide 231085 [N-Cyclohexyl-N-methyl-4-(1,2-dihydro-2-oxo-6quinolyloxy)butyramide; 

OPC 3689] 

A cell-permeable, selective inhibitor of PDE III (IC 50 = 70 nM). 

Denbufylline 253500 [1,3-Di-n-butyl-7-(2´-oxopropyl)xanthine] 

A cell-permeable, xanthine derivative that acts as a selective 

inhibitor of phosphodiesterase IV (PDE IV; K i ~ mM). 

0 mg $93 

500 mg $57 

0 mg $ 5 

5 mg $ 8 

Dipyridamole 322328 A cell-permeable, selective inhibitor of PDE V (IC 50 = 900 nM). 00 mg $34 

EHNA, Hydrochloride 324630 [erythro-9-(2-Hydroxy-3-nonyl)adenine, HCl] 

A cell-permeable, potent inhibitor of PDE II (IC 50 = 800 nM). Does not 

inhibit other PDE isozymes (IC 50 > 00 mM). 

Etazolate, Hydrochloride 331500 {1-Ethyl-4-[(1-methylethylidene)hydrazino]-1H-pyrazolo 

[3,4-b]pyridine-5-carboxylic Acid Ethyl Ester, HCl; SQ20009} 

A selective inhibitor of PDE IV (IC 50 = 2 mM). 

Classification of Phosphodiesterases 

PDE Regulatory Mechanism Tissue Distribution 

I Ca 2+ /CaM-stimulated Heart, brain, lung, smooth 

muscle 

II cGMP-stimulated Adrenals, heart, lung, liver, 

platelets 

III cGMP-inhibited, Heart, lung, liver, platelets, 

adipose tissue 

IV cAMP-specific Kidney, brain, liver, lung, Sertoli 

cells 

V cGMP-specific Lung, platelets, smooth muscle 

VI Photoreceptor cGMPspecific 

VII cAMP-specific, highaffinity,rolipraminsensitive 

VIII cAMP-selective, IBMX- 

insensitive 

IX cGMP-selective, IBMX 

insensitive 

Photoreceptors 

Skeletal muscle, heart, kidney, 

brain, pancreas, T cells 

Testes, eye, liver, skeletal 

muscle, heart, kidney, ovary, 

brain, T cells 

Kidney, liver, lung, brain 

X cGMP-sensitive Testes, brain 

XI cGMP-sensitive, dual- 

specificity 

Skeletal muscle, prostrate, 

kidney, liver, pituitary, salivary 

glands, testes 

More online... www.calbiochem.com/inhibitors/PDE 

0 mg $55 

5 mg $75 


Phone 800 628 8470 


57


Phosphodiesterase Inhibitors, continued 


3-Isobutyl- -methylxanthine 410957 (IBMX) 

8-Methoxymethyl-3-isobutyl- - 

methylxanthine 

4-{[3´,4´-(Methylenedioxy)benzyl] 

amino}-6-methoxyquinazoline 

A cell-permeable, non-specific inhibitor of cAMP and cGMP 

phosphodiesterases (IC 50 = 2–50 mM). 

454202 (8-Methoxymethyl-IBMX) 

A cell-permeable, selective inhibitor of PDE I (IC 50 = 4 mM). 

58 Orders Phone 800 854 34 7 


Fax 800 776 0999 


250 mg 

g 

$45 

$ 7 

0 mg $ 0 

475250 A potent and specific inhibitor of PDE V (IC 50 = 230 nM). mg $69 

Milrinone 475840 [1,6-Dihydro-2-methyl-6-oxo-(3,4´-bipyridine)-5-carbonitrile] 

A cell-permeable, selective inhibitor of PDE III (IC 50 = 300 nM). 

MY-5445 474925 [1-(3-Chlorophenylamino)-4-phenylphthalazine] 

A cell-permeable, selective inhibitor of PDE V (IC 50 = 600 nM). 

N Phosphodiesterase 4 Inhibitor 524717 [3,5-Dimethyl-1-(3-nitrophenyl)-1H-pyrazole-4-carboxylic acid ethyl 

ester] 

A high-affinity active site binding inhibitor of phosphodiesterases 

IVB and IVD (IC 50 = 33 and 2 nM, respectively). 

Phosphodiesterase V Inhibitor II 524714 (PDE V Inhibitor II) 

A cell-permeable, potent, and highly selective phosphodiesterase V 

inhibitor (IC 50 = 5 nM for bovine aorta PDE V; IC 50 > 0 mM for human 

recombinant PDE I & III, and for bovine aorta PDE II & IV). 

Ro-20- 724 557502 [4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone] 

A cell-permeable, selective inhibitor of PDE IV (IC 50 = 2 mM). 

Rolipram 557330 {4-[3-(Cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone} 

A cell-permeable, selective and competitive inhibitor of PDE IV 

(IC 50 = 800 nM). Does not inhibit PDE I or PDE II, even at 

00 mM. Only a weak inhibitor of PDE III (IC 50 = 00 mM). A rolipraminsensitive 

PDE IV subtype is also known to exist. 

Trequinsin, Hydrochloride 382425 [9,10-Dimethoxy-2-mesitylimino-3-methyl-2,3,6,7-tetrahydro-4Hpyrimido-(6,1-a)-isoquinolin-4-one, 

HCl; HL 725] 

A cell-permeable and extremely potent inhibitor of PDE III 

(IC 50 = 300 pM) and platelet aggregation in vitro. 

0 mg $ 75 

0 mg $ 7 

0 mg $ 29 

5 mg $84 

00 mg $6 

5 mg $ 28 

0 mg $ 82 

Vinpocetine 677500 A selective inhibitor of PDE I (IC 50 = 20 mM). 20 mg $67 

W-5, Hydrochloride 681625 [N-(6-Aminohexyl)-1-naphthalenesulfonamide, HCl] 

A cell-permeable, calmodulin antagonist that inhibits PDE I 

(IC 50 = 240 mM). 

W-7, Hydrochloride 681629 [N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, HCl] 

A calmodulin antagonist that inhibits PDE I (IC 50 = 28 mM). A cerebral 

vasodilator. 

W- 2, Hydrochloride 681635 [N-(4-Aminobutyl)-2-naphthalenesulfonamide, HCl] 

A calmodulin antagonist that inhibits PDE I (IC 50 = 260 mM). 

W- 3, Hydrochloride 681636 [N-(4-Aminobutyl)-5-chloro-2-naphthalenesulfonamide, HCl] 

A calmodulin antagonist that inhibits PDE I (IC 50 = 68 mM). 

Zaprinast 684500 {1,4-Dihydro-5-(2-propoxyphenyl)-7H-1,2,3-triazolo 

[4,5-d]pyrimidine-7-one; M&B22948} 

Phosphodiesterase Inhibitor Set I 

A cell-permeable, selective inhibitor of PDE V (IC 50 = 450 nM). Inhibits 

PDE IX at much higher concentrations (IC 50 = 35 mM). 

mg $77 

0 mg $77 

mg $77 

mg $77 

25 mg $49 

Provided as a set of 4 vials. Each set contains 0 mg of 8-Methoxymethyl-3-isobutyl- -methylxanthine (Cat. No. 454202), a Ca 2+ /CaM-dependent 

PDE (PDE I) inhibitor; mg of 4-{[3,4 -(Methylenedioxy)benzyl]amino}-6-methoxyquinazoline (Cat. No. 475250), a cGMP-specific PDE (PDE V) 

inhibitor; 5 mg of Rolipram (Cat. No. 557330), a cAMP-specific PDE (PDE IV) inhibitor; and 0 mg of Trequinsin, Hydrochloride (Cat. No. 382425), a 

cGMP-inhibited PDE (PDE III) inhibitor. 

Cat. No. 524718 1 set $347

Plasminogen Activator Inhibitors 

Tissue plasminogen activator (tPA) and urokinase 

plasminogen activator (uPA) and their inhibitor, 

plasminogen activator inhibitor 1 (PAI-1) are 

involved in the regulation of tissue morphogenesis 

and differentiation. Plasminogen activator-mediated 

extracellular matrix degradation plays an important 

role in the development of tumors and tumor metastasis. 

Over-expressed tPA and uPA systems are reported in 

patients with aggressive metastasizing tumors. Hence, 

inhibition of plasminogen activation is an important 

pharmacological target for blocking metastasis and 

reducing primary tumor growth. 

tPA is a serine protease that converts plasminogen to 

plasmin and can trigger the degradation of extracellular 

matrix proteins. The tPA/plasmin proteolytic system has 

been implicated in both physiological and pathological 

processes. In the brain tPA promotes events associated 

with synaptic plasticity such as motor learning and 

long-term potentiation. Under non-inflammatory 

conditions it also contributes to excitotoxic neuronal 

Plasminogen Activator Inhibitors 



death. Outside the nervous system tPA is mainly found 

in the blood, where it functions as a thrombolytic 

enzyme and prevents excess fibrin accumulation in 

vessels. 

PAI-1, a serine proteinase inhibitor, is a 50 kDa 

glycoprotein that acts as an important physiological 

inhibitor of tPA and uPA. It plays a crucial role in the 

regulation of vascular thrombosis, tumor invasion, 

neovascularization, and inflammation. Higher plasma 

levels of PAI-1 are correlated with an increased risk for 

cardiovascular diseases. 

References: 

Stabuc, B., et al. 2003. Oncology Reports 10, 635. 

Wang, Q., and Shaltiel, S. 2003. BMC Biochemistry 4, 5. 

Robert, C., et al. 999. Clin. Cancer Res. 5, 2094. 

Chintala, S.K. 996. Frontiers Biosci. 1, 324. 


Amiloride, Hydrochloride 129876 A competitive inhibitor of uPA activity (K i = 7 mM). 00 mg $4 

Plasminogen Activator Inhibitor- , 

Human, Recombinant 


Mutant, Human, Recombinant 


Mutant, Mouse, Recombinant 


Rat, Recombinant 

More online... www.calbiochem.com/inhibitors/PA 

528205 (PAI-1) 

Primary inhibitor of both tPA and uPA. PAI- is synthesized by 

vascular epithelium and hepatocytes. Used as a marker for acute 

myocardial infarction and in the diagnosis of several thrombolytic 

disorders. Elevated levels are found in subjects with accelerated 

coronary artery disease. May serve as an independent and strong 

prognostic factor in breast cancer patients. Patients having elevated 

levels of PAI- in their primary tumors are more prone to relapse. 

528208 (PAI-1, Mutant) 

Highly purified preparation of an altered form of human PAI- 

containing four mutated amino acids. Mutant PAI- is virtually 

unable to go latent and is stable at elevated temperature and pH for 

extended periods of time (t ½ = 45 h at 37˚C, pH 7.4). Inhibits uPA 

(K i = 5. x 0 6 M - sec - ) and tPA (K i = 7.9 x 0 5 M - sec - ). 

528213 (PAI-1) 

This inhibitor contains a single minor conservative amino acid 

substitution Ile 9 →Leu 9 that gives the inhibitor increased half life 

(about 4-fold increase over the native recombinant form). Stable 

when stored at or below pH 6.6. Has good stability with t ½ = 8–9 h 

at 25˚C, pH 7.4. 

528214 (PAI-1) 

Inhibits human uPA (K i = 6.3 x 0 6 M - sec - ). Stable when stored at or 

below pH 6.6. 

50 mg $200 

50 mg $ 95 

50 mg $ 95 

50 mg $ 95 


Phone 800 628 8470 


59


Protein Methtyltransferase Inhibitors 


N Protein Arginine 

539209 (PRMT Inhibitor, AMI-1) 

5 mg $95 

N-Methyltransferase 

Inhibitor, AMI- 

A cell-permeable, potent, specific and non-AdoMet (S-adenosyl-L-methionine, 

SAM)-competitive inhibitor of protein arginine N-methyltransferases (PRMTs; 

IC = 8.8 mM for PRMT and 3.03 for yeast-RMT p) with minimal effect on lysine 

50 

methyltransferases. 

N Protein Synthesis 539690 3,4,5,6-Tetrabromofluorescein 

25 mg $ 42 

Initiation Inhibitor, NSC 

9889 

A cell-permeable, AdoMet (SAM) competitive inhibitor of protein arginine and 

lysine methyltransferases (IC = .4 mM and 780 nM for human and yeast 

50 

arginine methyl transferases, respectively). 

Protein Synthesis Inhibitors 

Many inhibitors used to block protein synthesis are 

either antibiotics or toxins. Their mechanism of action 

includes the interruption of peptide-chain elongation, 

blocking the A site of ribosomes, and misreading 

Protein Synthesis Inhibitors 

of the genetic code. Some of them may also prevent 

the attachment of oligosaccharide side chains to 

glycoproteins. 


Anisomycin, Streptomyces 

griseolus 

Blasticidin S, Hydrochloride, 

Streptomyces griseochromogenes 

176880 [2-(p-Methoxybenzyl)-3,4-pyrrolidinediol-3-acetate] 

A reversible inhibitor of protein synthesis at the translation step. An 

activator of p38 and SAPK in mammalian cells. 

203350 Nucleoside antibiotic that specifically inhibits protein synthesis in 

both prokaryotes and eukaryotes. 

Chloramphenicol 220551 Inhibits protein synthesis by binding to the 50S ribosomal subunit 

and blocking the formation of the peptide bond by inhibiting peptidyl 

transferase activity. It is a potent inhibitor of mitochondrial protein 

synthesis in eukaryotic cells. 

Cycloheximide 239763 An antifungal antibiotic that inhibits protein synthesis in eukaryotes 

but not in prokaryotes. Interacts directly with the translocase 

enzyme, interfering with the translocation step. Inhibits cell-free 

protein synthesis in eukaryotes. 

InSolution Cycloheximide 239765 A 00 mg/ml DMSO solution (sterile-filtered) of cycloheximide 


Cycloheximide, High Purity 239764 An antifungal antibiotic that inhibits protein synthesis in eukaryotes 

but not in prokaryotes. Interacts directly with the translocase 

enzyme, interfering with the translocation step. Inhibits cell-free 

protein synthesis in eukaryotes. 

Emetine, Dihydrochloride 324693 (6´,7´,10,11-Tetramethoxyemetan, 2HCl) 

An irreversible inhibitor of protein synthesis in eukaryotes. Blocks 

the movement of ribosomes along the mRNA. 

Erythromycin, Streptomyces 

erythreus 

329815 (Erythromycin A) 

Inhibits bacterial protein synthesis by binding to 70S ribosomes 

and stimulating the dissociation of peptidyl-tRNA from ribosomes. 

Inhibits elongation of the protein by peptidyltransferase that forms 

peptide bonds between the amino acids, by preventing the ribosome 

from translocating down the mRNA. 

G 4 8 Sulfate, Cell Culture Tested 345810 An aminoglycoside antibiotic related to gentamycin that irreversibly 

binds to ribosomes and inhibits protein synthesis in prokaryotic and 

eukaryotes. 

KU = kilounits or 000 units; MU = million units 

More online... www.calbiochem.com/inhibitors/PS 

0 mg $45 

25 mg $98 

60 Orders Phone 800 854 34 7 


Fax 800 776 0999 


25 g 

00 g 

500 g 

g 

5 g 

00 mg 

g 

$39 

$ 4 

$499 

$57 

$ 68 

ml $59 

$34 

$ 22 

250 mg $53 

5 g 

25 g 

250 mg 

500 mg 

g 

5 g 

25 g 

$38 

$ 00 

$35 

$45 

$59 

$ 86 

$826

Protein Synthesis Inhibitors, continued 




G 4 8 Sulfate, Sterile-Filtered 

Aqueous Solution, Cell Culture 

Tested 

345812 An aminoglycoside antibiotic related to gentamycin that irreversibly 

binds to ribosomes and inhibits protein synthesis in prokaryotic and 

eukaryotes. Sterile-filtered solution of Cat. No. 3458 0 supplied at 

50 mg/ml. 

Hygromycin B, Streptomyces sp. 400051 An aminoglycoside antibiotic that blocks protein synthesis in 

prokaryotes and eukaryotes. 

Kanamycin Sulfate, Streptomyces 

kanamyceticus 

Kanamycin Sulfate, Streptomyces 

kanamyceticus, Cell Culture-Tested 

N Protein Synthesis Initiation 

Inhibitor, NSC 9889 

420311 (Kamycin) 

An inhibitor of protein biosynthesis that acts on the 70S ribosome, 

causing misreading of the genetic code. 

420411 An inhibitor of protein biosynthesis that acts on the 70S ribosome, 

causing misreading of the genetic code. 

539690 (3,4,5,6-Tetrabromofluorescein) 

A cell-permeable, AdoMet (SAM) competitive inhibitor of protein 

arginine and lysine methyltransferases (IC = .4 mM and 780 nM 

50 

for human and yeast arginine methyl transferases, respectively). 

Puromycin, Dihydrochloride 540222 [3´-(a-Amino-p-methoxyhydrocinnamamido)-3´-deoxy-N,Ndimethyladenosine, 

2HCl] 

An aminonucleoside antibiotic that acts as a prokaryotic and 

eukaryotic protein synthesis inhibitor. Resembles the aminoacyladenylyl 

terminus of aminoacyl-tRNA and competes for binding to 

the ”A site“ of the large ribosomal subunit. 

Puromycin, Dihydrochloride, Cell 

Culture-Tested 

Spectinomycin, Dihydrochloride, 

Pentahydrate, Streptomyces sp. 

Streptomycin Sulfate, 


540411 An aminonucleoside antibiotic that acts as a prokaryotic and 

eukaryotic protein synthesis inhibitor. Resembles the aminoacyladenylyl 

terminus of aminoacyl-tRNA and competes for binding to 

the ”A site“ of the large ribosomal subunit. 

567570 Inhibits protein synthesis by binding to the 30S ribosomal subunit to 

prevent the formation of an initiation complex with messenger RNA. 

5711 Binds irreversibly to the 30S subunit of bacterial ribosomes and 

prevent the 50S ribosomal subunit from attaching to the translation 

initiation complex. Inhibits initiation, elongation, and termination 

of protein synthesis in prokaryotes and induces misreading of the 

genetic code. 

Tetracycline, Hydrochloride 58346 An antibiotic that inhibits bacterial protein synthesis by reversibly 

binding to the 30S ribosomal subunit, preventing binding of 

aminoacyl tRNA to the A-site and blocking translocation. 

Tetracycline, Hydrochloride, Cell 

Culture-Tested 

583411 An antibiotic that inhibits bacterial protein synthesis by reversibly 

binding to the 30S ribosomal subunit, preventing binding of 

aminoacyl tRNA to the A-site and blocking translocation. 

Thiostrepton 598226 Inhibits bacterial protein synthesis and ribosomal GTPase activity by 

binding non-covalently, but virtually irreversibly, to the 23S rRNA in 

the GTPase center of the 50S subunit. Thiostrepton binding directly 

prevents elongation factor G binding to the ribosome. 

Tobramycin, Free Base 614005 Binds irreversibly to the 30S subunit of bacterial ribosomes and 

prevents the 50S ribosomal subunit from attaching to the translation 

initiation complex. 

0 ml 

20 ml 

50 ml 

00 KU 

MU 

5 MU 

0 MU 

5 g 

25 g 

5 g 

25 g 

$50 

$90 

$ 6 

$39 

$ 22 

$478 

$849 

$50 

$ 95 

$60 

$225 

25 mg $ 42 

25 mg 

00 mg 

25 mg 

00 mg 

$39 

$ 37 

$48 

$ 57 

0 g $ 2 

00 g $47 

0 g 

25 g 

50 g 

0 g 

25 g 

50 g 

g 

0 g 

$29 

$39 

$72 

$39 

$57 

$ 0 

$76 

$504 

00 mg $49 


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6


Sonic Hedgehog Signaling Inhibitors 

Mammalian Hedgehog proteins include Sonic Hedgehog 

(Shh), Indian Hedgehog (Ihh), and Desert Hedgehog (Dhh). 

Shh is expressed mainly in the epithelia in the tooth, hair, 

whisker, gut, bladder, urethra, vas deferens, and lung, Dhh 

is found in Schwann and Sertoli cell precursors and Ihh is 

expressed in gut and cartilage. Hedgehog proteins undergo 

autocatalysis to generate a ~20 kDa N-terminal domain 

and a ~25 kDa C-terminal domain. This autoprocessing 

causes the covalent attachment of cholesterol onto the 

carboxy-terminus of the N-terminal domain. The Nterminal 

domain retains all signaling capabilities while the 

C-terminal domain is responsible for the intramolecular 

precursor processing. The cholesterol moiety is believed 

to be responsible for directing Hedgehog traffic in the 

secretory cell. 

Shh, a secreted morphogen, has been implicated in several 

embryonic developmental processes. It displays inductive, 

proliferative, neurotrophic, and neuroprotective properties. 

Shh often works in concert with the Wnt signaling protein 

in setting embryonic patterns. The Wnt pathway uses bcatenin 

to transduce its signals to the nucleus; however, 

the Shh pathway utilizes a 155 amino acid protein, Cubitus 

interruptus (Ci155) in Drosophila or Gli in mammals. In 

the absence of a Shh signal, Ci is targeted for proteolysis, 

which generates a truncated 75-amino acid residues form 

(Ci75) that acts as a transcriptional repressor. In vertebrates 

three Gli proteins (Gli1, Gli2, and Gli3) have been reported. 

Despite several homologous regions, including a DNAbinding 

domain with five C2-H2 zinc fingers and a Cterminal 

transcription activation domain, these proteins 

have distinct activities and are not considered to be 

functionally equivalent. 

Sonic Hedgehog Signaling Inhibitors 

Shh signaling is known to occur through a receptor 

complex associating two membrane proteins, Patched (Ptc) 

and Smoothened (Smo). Ptc is a twelve-pass membrane 

protein that acts as a receptor and binds Hedgehog ligand; 

Smo is a seven-pass membrane protein that acts as a signal 

transducer. In the absence of a ligand, Ptc interacts with 

Smo and inhibits its activity. Shh binding to Ptc removes 

the inhibitory effect and allows Gli to enter the nucleus and 

act as a transcriptional activator. Shh signaling is required 

throughout embryonic development and is involved in the 

determination of cell fate and embryonic patterning during 

early vertebrate development. During the late stage of 

development, Shh is involved in the proper formation of a 

variety of tissues and organs. Shh also functions with other 

signaling molecules such as the fibroblast growth factors 

and bone morphogenetic protein to mediate developmental 

processes. Mutations in any of the components of the 

Shh pathway can lead to congenital defects and diseases, 

including cancer. Hence, the Shh pathway has become a 

potential target for drug development for the treatment of 

cancers and degenerative diseases. 

References: 

Lum, L., and Beachy, P.A. 2004. Science 304, 755. 

Wetmore, C. 2003. Curr. Opin. Genet. Dev. 13, 34. 

Pola, R., et al. 200 . Nat. Med. 7, 706. 

Chuong, C.M., et al. 2000. Cell. Mol. Life Sci.57, 692. 

McMahon, A.P. 2000. Cell 100, 85. 

Pepinsky, R.B., et al. 998. J. Biol. Chem. 273, 4037. 

Porter, J.A., et al. 996. Science 274, 255. 

More online... www.calbiochem.com/inhibitors/Shh 


AY 9944 190080 A cell-permeable inhibitor of 7-dehydrocholesterol reductase 

(D7-sterol reductase). Also reported to induce a rapid and irreversible 

reduction in acidic-sphingomyelinase activity in fibroblasts. 

Cyclopamine, V. californicum 239803 A steroidal alkaloid and cholesterol mimic that disrupts cholesterol 

bio-synthesis and specifically antagonizes Shh signaling through 

direct interaction with Smo (smoothened). 

N Cyclopamine-KAAD 239804 [KAAD-Cyclopamine; 3-Keto-N-(aminoethyl-aminocaproyl-dihydro- 

cinnamoyl)cyclopamine] 

A potent, cell-permeable analog of Cyclopamine (Cat. No. 239803) 

that inhibits the Hedgehog signaling with similar or lower toxicity 

(IC 50 = 20 nM in Shh-LIGHT2 assay). 

Jervine 420210 [(3b, 23b)-17,23-Epoxy-3-hydroxyveratraman-11-one; 11- 

Ketocyclopamine] 

A cell-permeable inhibitor that induces cyclopia by blocking Shh 

signaling (IC 50 = 500 –700 nM in S 2 cells). 

5 mg $ 5 

mg $ 2 

00 mg $ 32 

mg $95 

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Sonic Hedgehog Signaling Inhibitors, continued 




SANT- 559303 A potent antagonist of the Shh signaling (IC 50 = 20 nM in the Shh- 

LIGHT2 assay and in Ptch -l- cells) that acts by binding directly 

to Smoothened (Smo; K d = .2 nM). Unlike cyclopamine (Cat. No. 

239803), SANT- equipotently inhibits the activities of both wildtype 

and oncogenic Smo (IC 50 = 30 nM in SmoA -LIGHT2 assay). 

Tomatidine, HCl 614350 A steroidal alkaloid that structurally resembles Cyclopamine (Cat. No. 

239803), but lacks the capacity to inhibit Shh signaling. 

U 8666A 662015 [3b-(2-Diethylaminoethoxy)androst-5-en-17-one, HCl] 

A cell-permeable, amphiphilic amino-steroid that alters intracellular 

membrane protein trafficking by impairing intracellular biosynthesis 

and transport of LDL-derived cholesterol, presumably via its 

inhibitory effect on 2,3-oxidosqualene-lanosterol cyclase activity. 

Also reported to inhibit the activity of D8-sterol isomerase. 

Stem Cell Proliferation Inhibitors 


Stem Cell Proliferation Inhibitor 569620 (Ac-SDKP; Goralatide; Seraspenide) 

A tetrapeptide that acts as a natural inhibitor of pluripotent 

hematopoietic stem cell proliferation. Protects bone marrow 

against chemotherapeutic agents, ionizing radiations, hyperthermy, 

or phototherapy-induced toxicity. Inhibits cardiac fibroblast 

proliferation, collagen synthesis, and activation of p42/p44 MAP 

kinases. Cleaved to an inactive form by angiotensin I-converting 

enzyme (ACE). 

Tautomerase Inhibitor 

To view all Stem Cell-related antibodies, growth factors, 

and cell culture reagents, visit our Stem Cell Resource at 

www.calbiochem.com/stemcells 

5 mg $ 28 


N MIF Antagonist, ISO- 475837 [(S,R)-3-(4-Hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid, 

methyl ester; Macrophage Migration Inhibitory Factor Antagonist, ISO-1] 

A cell-permeable isoxazoline compound that displays antiinflammatory 

properties. Inhibits MIF tautomerase activity by 

binding to its catalytic active site (IC 50 = 7 mM for D-dopachrome 

tautomerase) and suppresses the production of TNFa, PGE 2 , and 

COX-2 in human monocytes, and arachidonic acid in RAW 264.7 

macrophages. Shown to exhibit antidiabetogenic properties in 

immunoinflammatory diabetic mouse model. 

5 mg $ 09 

25 mg $47 

0 mg $90 

5 mg $82 


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63

Inhibitors: Some Technical Tips 


How much inhibitor should I use? 

The amount of inhibitor required depends on various factors, such as target accessibility, cell permeability, duration of incubation, 

type of cells used, and others. We recommend surveying the literature to determine the initial concentration. If published K i or IC 50 

values are known, use 5–10 times higher inhibitor amounts than these values to maximally inhibit enzyme activity. If K i or IC 50 values 

are unknown, then try a wide range of inhibitor concentrations and use Michaelis-Menten kinetics to determine the K i value. It is not 

unusual to see either no inhibition or even a reverse effect when high concentrations of inhibitors are used. Always run an appropriate 

control to eliminate non-specific effects of the solvent used to solubilize the inhibitor. 

What is the difference between EC 50 , ED 50 , K i , IC 50 , and K d , pIC 50 ? 

In pharmacology and biochemistry, the following terms are commonly used to determine the efficacy of a drug or inhibitor. 

Sometimes, confusion arises when researchers try to repeat experiments without considering the exact term used by the original 

investigators. 

EC 50 : Clinical efficacy of a drug (concentration required) to produce 50% of the maximum effect (may be inhibitory or 

stimulatory effect). This term is used usually with pharmaceuticals. 

ED 50 : Median effective dose (as opposed to concentration) at which 50% of individuals exhibit the specified quantal effect. 

IC 50 : Concentration required to produce 50% inhibition. 

K i : Inhibitor concentration at which 50% inhibition is observed (it is calculated using Michaelis-Menten kinetics). 

K d : An equilibrium constant for the dissociation of a complex of two or more biomolecules into its components; for 

example, pIC 50 dissociation of an inhibitor or substrate from an enzyme. 

pIC 50 : The negative logarithm to base 10 of the IC 50 . 

How much inhibitor or stimulator should be injected into an animal? 

There is no simple answer to this question. Optimize the dose empirically by performing a few preliminary experiments. First 

determine if the compound in question is cell-permeable. Also, survey the literature for any reported IC 50 , ED 50 , or EC 50 , values. 

Follow the sample calculation given below as a general guide: 

H-89, dihydrochloride, a cell-permeable protein kinase A inhibitor, has an IC 50 value of 48 nM. It has a molecular weight of 519.3. 

For H-89, 2HCl a 240-480 nM range of H-89 is sufficient to cause maximal inactivation of protein kinase A. To use it in vivo 

we have to make a few assumptions. If a rat weighs about 200 g and we assume that 70% of its body weight is water, the volume 

of distribution will be approximately 140 ml. In this case 240 nM = 240 nmoles/liter = 124.63 mg/liter. Because the volume of 

distribution is about 140 ml, 124.63 × 0.140 = 17.45 mg would be the required amount for injection into the rat. It is important 

to note that the drug distribution will vary depending on the mode of injection (intravenous, intramuscular, or intraperitoneal), 

bioavailability, half-life, rates of hepatic and renal clearance, binding to proteins, and tissue-specific distribution and accumulation. 

The specific tissue uptake may also be limited in whole organs or tissues as compared to isolated cell preparations. In 

whole animal studies, sometimes a loading dose is required to achieve the target concentration. This may then be followed by a 

sustained infusion to maintain the drug level in the blood. One must always exercise caution and not overdose the animal. 

What type of solvent is best suited for dissolving an inhibitor? 

In biological experiments water is the most preferred solvent. However, several organic compounds are either not soluble in 

water or they degrade rapidly in the presence of moisture. If DMSO is a recommended solvent, use a fresh stock bottle of DMSO 

that is deemed free of any moisture. Any contaminating moisture may accelerate the degradation of compound in 

question or may render it insoluble. 

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Why can’t I make serial dilutions of my DMSO stock solution directly in my buffer? 



In some cases this may not be a problem. However, in most cases the organic material will precipitate out of the solution when 

added directly to an aqueous medium. It is best to make the initial serial dilutions only in DMSO and then add the final diluted 

sample to your buffer or the cell culture medium. Also, the compound may be soluble in aqueous medium only at its working 

concentration. 

Which protein kinase inhibitor is best suited for my experiment? 

If the mechanism involved in phosphorylation is unknown, a broad range inhibitor, such as Staurosporine, should be used 

first to determine if indeed a protein kinase is involved. Secondly, a more specific inhibitor of PKA (e.g., H-89, Cat. No. 371963, or 

8-Br-cAMP, Rp isomer, Cat. No. 116816), PKC (e.g., Bisindolylmaleimide, Cat. No. 203290), or PKG (e.g., KT5823, Cat. No. 420321; 

or PKG inhibitor, Cat. No. 370654) should be used to eliminate the possibility of more than one kinase. To elucidate the exact 

mechanism involved, isozyme specific inhibitors, such as for PKC isozymes, can be used. 

How can I determine if a caspase inhibitor is reversible or irreversible? 

The C-terminal group determines the reversibility or the irreversibility of any caspase inhibitor. In general, caspase inhibitors 

with an aldehyde (CHO) group are reversible. The CMK, FMK, and FAOM groups are more reactive and form covalent bonds with 

the enzyme, creating an irreversible linkage. FMK is slightly less reactive than CMK and therefore is considered more specific 

for the enzyme site being inhibited. 

What determines the specificity of a particular caspase inhibitor? 

The peptide recognition sequence determines the specificity of the inhibitor for a particular caspase. Sometimes the aspartic acid 

residue is esterified to increase cell permeability of the peptide. VAD is a general caspase inhibitor. Earlier it was considered to be 

specific for caspase-1 (ICE), however, now it is considered to inhibit even caspase-3 and caspase-4. Addition of a tyrosine residue 

(Y) to the sequence (YVAD) makes the inhibitor more specific for caspase-1. The sequence DEVD recognizes caspase-3 and also 

caspases-6, -7, -8, and -10. 

What are the advantages of using FMK-based caspase inhibitors and how do they differ from 

CHO-based inhibitors? 

The FMK-based caspase inhibitors covalently modify the thiol group of the enzyme making them irreversible inhibitors. 

Generally, at the amine end of the inhibitor we have a benzyloxycarbonyl (Z), biotin, or aceytl (Ac) group. These groups also 

increase hydrophobicity of the molecule, which makes them more cell-permeable. Compared to the inhibitors with an Ac or a 

biotin group, those inhibitors with a Z-group are even more cell-permeable. Inhibitors with a biotin group can serve as a 

detection tool and are useful in tagging the enzyme-inhibitor site. 

The CHO-based inhibitors are reversible due to the fact that the thiol group of the enzyme forms an adduct to the carbonyl group 

of the aldehyde that is reversible. As a general rule CHO-based inhibitors are hydrated and hence are slow binding. The extent of 

their reversibility depends on the pH, metal ion concentration, and other conditions. When the aldehyde group is attached to the 

aspartic acid (D-CHO), the product exists as a pseudo acid aldehyde in equilibrium. This makes it somewhat cell-permeable. 

What criteria should I use when selecting a protease inhibitor? 

When processing cells or tissues assume that active proteases are present in the medium or are being secreted. Hence, 

it is important to include protease inhibitors even in the early steps of sample preparation. For best results add protease inhibitors 

to the medium just prior to use. Use of inhibitors in buffers stored over a period of time is not recommended. Different cells and 

tissue types exhibit different protease profiles. Serine proteases are widely distributed in all cells, bacterial cells contain higher 

levels of serine and metalloproteases; animal tissue extracts are rich in serine-, cysteine-, and metalloproteases, and plant 

extracts contain higher quantities of serine and cysteine proteases. Additionally, it is important to avoid EDTA when preparing 

extracts for IMAC (e.g., His•Tag® purification). If you are not sure of the type of proteases present in the sample, it is best to use 

or customize your own cocktails. 

Looking for more information? 

Keep up to date at our Inhibitor Resource 

www.calbiochem.com/inhibitors 


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65

Index 

Alphabetical Index 

400W .................................................................................... 0 

400W, Immobilized .......................................................... 0 

A 

A3, Hydrochloride ..............................................9, 29, 33, 43 

A77 726 .................................................................................46 

AACOCF 3 ..................................................................................93 

7-AAG ................................................................................. 49 

Ab 40 Fibrillogenesis Inhibitor .............................................96 

Ab 42 Fibrillogenesis Inhibitor I ...........................................96 

Ab 42 Fibrillogenesis Inhibitor II .........................................96 

Ab 42 Fibrillogenesis Inhibitor III ........................................96 

Ab 42 Fibrillogenesis Inhibitor IV ........................................96 

ACA ...........................................................................................93 

Acetyl- -keto-b-Boswellic Acid, 

Boswellia serrata ......................................................82, 9 

N-Acetyl-S-farnesyl-L-cysteine ..................................... 44 

N-Acetyl-S-geranylgeranyl-L-cysteine (AGGC) ........ 44 

Acetyl-Pepstatin ................................................................. 25 

Actinomycin D, 7-Amino-...................................................72 

Actinomycin D, Streptomyces sp. .....................................72 

AdaAhX 3 L 3 VS ........................................................................ 37 

AdaLys(bio)AhX 3 L 3 VS ......................................................... 37 

Adenosine ............................................................................. 4 

Adenosine 3´,5´-cyclic Monophosphorothioate, 

2´-O-Monobutyryl-, Rp-Isomer, Sodium Salt .........34 


8-Bromo-, Rp-Isomer, Sodium Salt ...........................33 


8-Bromo-2´-monobutyryl-, Rp-Isomer, 

Sodium Salt ......................................................................33 


8-Chloro-, Rp-Isomer, Sodium Salt ...........................33 


Rp-Isomer, Triethylammonium Salt ...........................33 

Adenylyl Cyclase Toxins Inhibitor .................................. 39 

Adenylyl Cyclase Type V Inhibitor, NKY80................... 39 

ADP-HPD, Dihydrate, Ammonium Salt ............................79 

AEBSF, Hydrochloride ........................................................ 25 

AEBSF, Immobilized ........................................................... 25 

AG 9 ..........................................................................................46 

AG 7 ........................................................................................46 

AG 8 ........................................................................................46 

AG 30 ........................................................................................46 

AG 43 ........................................................................................46 

AG 82 ........................................................................................46 

AG 99 ........................................................................................46 

AG 2 ......................................................................................46 

AG 26 .....................................................................................25 

AG 83 .....................................................................................46 

AG 2 3 .....................................................................................46 

AG 490 .....................................................................................46 

AG 490, m-CF 3 .......................................................................46 

AG 494 .....................................................................................47 

AG 527 .....................................................................................47 

AG 537, Bis-Tyrphostin ........................................................47 

AG 538 .....................................................................................47 

I-OMe-AG 538 .......................................................................47 

AG 555 .....................................................................................47 

AG 556 .....................................................................................47 

AG 592 .....................................................................................47 

AG 825 .....................................................................................47 

AG 835 .....................................................................................47 

AG 879 .....................................................................................47 

AG 957 .....................................................................................47 

AG 957, Adamantyl Ester ....................................................47 

AG 024 ...................................................................................47 

AG 295 ...................................................................................47 

AG 296 ...................................................................................48 

AG 387 ............................................................................48, 82 

AG 433 ...................................................................................48 

AG 478 ...................................................................................48 

InSolution AG 478 ...........................................................48 

AGL 2043 .................................................................................48 

AGL 2263 .................................................................................48 

Akt Inhibitor .............................................................................4 

Akt Inhibitor II ..........................................................................4 

Akt Inhibitor III ........................................................................4 

Akt Inhibitor IV ........................................................................4 

InSolution Akt Inhibitor IV ................................................4 

Akt Inhibitor V, Triciribine.....................................................4 

Akt Inhibitor VI, Akt-in ..........................................................4 

Akt Inhibitor VII, TAT-Akt-in ................................................4 

Akt Inhibitor VIII, Isozyme-Selective, Akti- /2 ...............4 

InSolution Akt Inhibitor VIII, Isozyme-Selective, 

Akti- /2 ...............................................................................4 

Akt Inhibitor IX, API-59CJ-OMe .........................................4 

Akt Inhibitor X ..........................................................................5 

ALLM ............................................................................. 5, 25 

ALLN ................................................................... 5, 25, 37 

InSolution ALLN ...................................................... 5, 25 

Aloisine A.......................................................................... 5, 9 

Aloisine, RP 06 ............................................................... 5, 9 

Alsterpaullone ................................................................. 5, 9 

Alsterpaullone, 2-Cyanoethyl .................................... 5, 9 

a-Amanitin, Amanita sp. ....................................................72 

Methyl a-Amanitin Oleate .................................................72 

Amastatin, Streptomyces sp. ........................................... 25 

Amiloride, Hydrochloride ........................................ 4 , 59 

3-Aminobenzamide ..............................................................79 

e-Amino-n-caproic Acid .................................................. 25 

Aminogenistein ......................................................................48 

Aminoguanidine, Hemisulfate ......................................... 0 


p-Toluenesulfonate ...................................................... 0 

5-Aminoisoquinolinone, Hydrochloride ..........................79 

4-Amino- ,8-naphthalimide .............................................79 

Aminopeptidase N Inhibitor ............................................ 26 

Aminopurvalanol A ............................................................... 5 

AMO 6 8 ...............................................................................95 

AMPK Inhibitor, Compound C ..............................................5 

InSolution AMPK Inhibitor, Compound C ...............5, 84 

Anacardic Acid .......................................................................73 

Angiogenesis Inhibitor .........................................................48 

Angiotensin II, Human ...................................................... 39 

Anisomycin, Streptomyces griseolus ............................. 60 

Anthrax Lethal Factor, Recombinant, 

Bacillus anthracis............................................................25 

Anthrax Lethal Factor Protease Inhibitor, 

In-2-LF ............................................................................. 3 

Anthrax Lethal Factor Protease Inhibitor III ................ 3 

a -Antichymotrypsin, Human Plasma.......................... 26 

Antipain, Dihydrochloride ................................................ 26 

Antipain, Hydrochloride ................................................... 26 

a 2 -Antiplasmin, Human Plasma .................................... 26 

Antithrombin III, Human Plasma ................................... 26 

a -Antitrypsin, Human Plasma ............................. 8, 26 

Aphidicolin ..............................................................................72 

Apicidin, Fusarium sp. ..........................................................73 

Apoptosis Inhibitor ...............................................................67 

Apoptosis Inhibitor II, NS3694 ..........................................67 

Aprotinin, Bovine, Recombinant, Nicotiana sp. 

Animal-Free ................................................................... 26 

Aprotinin, Bovine Lung, Crystalline ............................... 26 

Aprotinin, Bovine Lung, Solution ................................... 26 

Arachidonylserotonin ....................................................88, 9 

H-Arg-Gly-Asp-OH ...............................................................70 

H-Arg-Gly-Asp-Ser-OH .......................................................70 

Aristolochic Acid ...................................................................93 

Aromatase Inhibitor I ........................................................ 4 

ATBI, Synthetic .................................................................... 26 

Atractyloside, Dipotassium Salt, 

Atractylis gummifera .................................................. 5 

Atrial Natriuretic Factor -28, Rat ............................... 4 

Aurintricarboxylic Acid .................................................77, 82 

Australine, Hydrochloride, 

Castanospermum australe......................................... 47 

Autocamtide-2 Related Inhibitory Peptide ......................7 

Autocamtide-2 Related Inhibitory Peptide II ..................7 

Autocamtide-2 Related Inhibitory Peptide II, 

Cell-permeable ..................................................................7 

Autocamtide-2 Related Inhibitory Peptide, 

Myristoylated .....................................................................7 

AY 9944................................................................................. 62 

5-Aza-2´-Deoxycytidine .....................................................7 

-Azakenpaullone ................................................................. 9 

3´-Azido-3´-deoxythymidine .............................................80 

InSolution AZT, Triphosphate,Tetralithium Salt .........80 

B 

Bafilomycin A , Streptomyces griseus ................ 0 , 42 

Baicalein ..................................................................................9 

Bax Channel Blocker ............................................................67 

Bax-Inhibiting Peptide, Negative Control ......................67 

Bax-Inhibiting Peptide, V5 .................................................67 

BAY -7082 ................................................................. 70, 54 

InSolution BAY -7082 ................................................ 54 

BAY -7085 ................................................................. 70, 54 

Bcr-abl Inhibitor ....................................................................48 

BEC, Hydrochloride ............................................................ 04 

Benzamidine, Hydrochloride ........................................... 26 

Benzyl-2-acetamido-2-deoxy-a- 

D-galactopyranoside ................................................... 47 

BER Pathway Inhibitor (DNA Base Excision Repair 

Pathway Inhibitor) ..........................................................77 

Bestatin ................................................................................. 26 

Bestatin Methyl Ester ....................................................... 26 

BHQ ........................................................................................ 42 

Bisindolylmaleimide I ...........................................................37 

InSolution Bisindolylmaleimide I ...................................37 

Bisindolylmaleimide I, Hydrochloride ..............................37 

Bisindolylmaleimide II..........................................................37 

Bisindolylmaleimide III, Hydrochloride ...........................37 

Bisindolylmaleimide IV ........................................................37 

Bisindolylmaleimide V..........................................................37 

Bisindolylmaleimide Inhibitor Set ....................................42 

Blasticidin S, Hydrochloride, Streptomyces 

griseochromogenes ..................................................... 60 

(—)-Blebbistatin .................................................................. 42 

(+)-Blebbistatin .................................................................. 42 

(±)-Blebbistatin .................................................................. 42 

InSolution Blebbistatin, Racemic ................................ 42 

Bohemine................................................................................. 5 

Bongkrekic Acid, Triammonium Salt ............................. 5 

BPDQ .........................................................................................48 

BPIQ-I .......................................................................................48 

BPIQ-II ......................................................................................48 

bpV(bipy) ..................................................................................59 

bpV(HOpic) ..............................................................................59 

bpV(phen) ................................................................................59 

bpV(pic) ....................................................................................59 

Bromocriptine Mesylate .................................................... 0 

BTS .......................................................................................... 42 

Bufalin ................................................................................... 42 

2,3-Butanedione 2-Monoxime ....................................... 42 

Butein .......................................................................................48 

N-(n-Butyl)deoxygalactonojirimycin ............................ 47 

N-Butyldeoxynojirimycin, Hydrochloride .................... 47 

C 

CA-074 .................................................................................. 27 

CA-074 Me ........................................................................... 27 

Caffeic Acid.......................................................... 9 , 05, 8 

Calcineurin Autoinhibitory Peptide ..................................59 

Calcineurin Autoinhibitory Peptide, 

Cell-permeable ................................................................59 

Calmidazolium Chloride .......................................... 42, 57 

Calmodulin Binding Domain ................................................7 

[Ala 286 ]-Ca 2+ /Calmodulin Kinase II 

Inhibitor 28 -30 .............................................................7 

Ca 2+ /Calmodulin Kinase II Inhibitor 28 -309 .................7 

Calmodulin Kinase IINtide ....................................................7 

Calmodulin Kinase IINtide, Myristoylated .......................7 

Calpain Activity Assay Kit, Fluorogenic ........................ 6 

Calpain Inhibitor III ............................................................ 5 

Calpain Inhibitor IV ............................................................ 5 

Calpain Inhibitor V .............................................................. 5 

Calpain Inhibitor VI ............................................................ 5 

Calpain Inhibitor X .............................................................. 5 

Calpain Inhibitor XI ............................................................ 5 

Calpain Inhibitor XII ........................................................... 5 

Calpain Inhibitor Set .......................................................... 6 

Calpain Substrate II, Fluorogenic ................................... 6 

Calpain Substrate III, Fluorogenic .................................. 6 

Calpain- Substrate, Fluorogenic ................................... 6 

Calpain- Substrate II, Fluorogenic ............................... 6 

Calpastatin Peptide............................................................. 5 

Calpastatin Peptide, Negative Control .......................... 5 

Calpastatin, Human Erythrocytes ................................... 5 

66 Orders Phone 800 854 34 7 


Fax 800 776 0999 


Calpastatin, Human, Recombinant, Domain I ... 5, 27 

Calpeptin ..................................................................... 5, 27 

Calphostin C, Cladosporium cladosporioides ................37 

Calyculin A, Discodermia calyx .........................................59 

Camptothecin, 0-Hydroxy-, 

Camptotheca acuminata ..............................................82 

Camptothecin, Camptotheca acuminata........................82 

Cantharidic Acid ....................................................................59 

Cantharidin .............................................................................59 

CAPE ....................................................................................... 54 

(E)-Capsaicin ....................................................................... 54 

Captopril ............................................................................... 4 

Carbonyl Cyanide m-Chlorophenylhydrazone ........... 5 

Carboxyatractyloside, Atractylis gummifera .............. 5 

Carboxypeptidase Inhibitor, Potato ............................... 27 

Cardiotoxin, Naja nigricollis ...............................................37 

Casein Kinase I Inhibitor, D4476 ........................................9 

InSolution Casein Kinase I Inhibitor, D4476..........9, 84 

Casein Kinase II Inhibitor I ...................................................9 

InSolution Casein Kinase II Inhibitor I ...........................9 

Casein Kinase II Inhibitor II, DMAT ....................................9 

InSolution Casein Kinase II Inhibitor, DMAT..........9, 84 

Caspase Inhibitor I ................................................................64 

InSolution Caspase Inhibitor I ........................................64 

Caspase Inhibitor I, Biotin Conjugate..............................64 

Caspase Inhibitor II ...............................................................64 


Caspase Inhibitor II, Cell-Permeable ................................64 

Caspase Inhibitor III .............................................................64 

Caspase Inhibitor IV .............................................................64 

Caspase Inhibitor VI .............................................................64 

InSolution Caspase Inhibitor VI......................................64 

Caspase Inhibitor VIII ...........................................................64 

Caspase Inhibitor X ...............................................................64 

Caspase Inhibitor Set I.........................................................66 

Caspase Inhibitor Set II .......................................................66 

Caspase Inhibitor Set III ......................................................66 

Caspase Inhibitor Set IV ......................................................66 

Caspase Inhibitor, Negative Control ................................64 

Caspase- Inhibitor I............................................................64 

Caspase- Inhibitor II ..........................................................64 

Caspase- Inhibitor II, Cell-Permeable ...........................64 

Caspase- Inhibitor II, Biotin Conjugate ........................64 

Caspase- Inhibitor IV .........................................................64 

Caspase- Inhibitor V ..........................................................64 

Caspase- Inhibitor VI .........................................................64 

Caspase-2 Inhibitor I............................................................64 

Caspase-2 Inhibitor II ..........................................................64 


Caspase-3 Inhibitor I, Biotin Conjugate .........................64 

Caspase-3 Inhibitor I, Cell-Permeable ............................64 

InSolution Caspase-3 Inhibitor I, Cell-Permeable ....64 

Caspase-3 Inhibitor II ..........................................................64 

InSolution Caspase-3 Inhibitor II ..................................64 

Caspase-3 Inhibitor II, Biotin Conjugate ........................64 

Caspase-3 Inhibitor III .........................................................64 

Caspase-3 Inhibitor IV .........................................................64 

Caspase-3 Inhibitor V ..........................................................64 

Caspase-3 Inhibitor VII ........................................................65 

Caspase-3/7 Inhibitor I ........................................................65 

Caspase-3/7 Inhibitor II ......................................................65 


Caspase-4 Inhibitor I, Cell-Permeable ............................65 



Caspase-6 Inhibitor II, Cell-Permeable ...........................65 

Caspase-8 Inhibitor I, Cell-Permeable .....................65, 66 

Caspase-8 Inhibitor II ...................................................65, 66 

InSolution Caspase-8 Inhibitor II ...........................65, 66 


InSolution Caspase-9 Inhibitor I ....................................65 

Caspase-9 Inhibitor II, Cell-Permeable ...........................65 

Caspase-9 Inhibitor III .........................................................65 

Caspase- 3 Inhibitor I .........................................................65 

Caspase- 3 Inhibitor II ........................................................65 

Castanospermine, Castanospermum australe ............ 47 

Cathepsin B Inhibitor I ..................................................... 27 

Cathepsin B Inhibitor II .................................................... 27 

Cathepsin G Inhibitor I ..................................................... 27 

Cathepsin Inhibitor I ......................................................... 27 

Cathepsin Inhibitor II ........................................................ 27 

Cathepsin Inhibitor III ....................................................... 27 


Cathepsin K Inhibitor I...................................................... 27 

Cathepsin K Inhibitor II .................................................... 27 

Cathepsin K Inhibitor III ................................................... 27 

Cathepsin L Inhibitor I ...................................................... 27 

Cathepsin L Inhibitor II ..................................................... 27 

Cathepsin L Inhibitor III.................................................... 27 

Cathepsin L Inhibitor IV.................................................... 28 

Cathepsin L Inhibitor V ..................................................... 28 

Cathepsin L Inhibitor VI.................................................... 28 

Cathepsin S Inhibitor ........................................................ 28 

Cathepsin/Subtilisin Inhibitor ......................................... 28 

CDC25 Phosphatase Inhibitor, BN82002 ........................59 

CDC25 Phosphatase Inhibitor, NSC 663284 ..................59 

Cdc2-Like Kinase Inhibitor, TG003 ................................... 5 

Cdk Inhibitor, p35.................................................................. 5 

Cdk Inhibitor ........................................................................ 5 

Cdk Inhibitor III ................................................................... 5 

Cdk Inhibitor, CGP745 4A ................................................ 5 

Cdk /2 Inhibitor II, NU6 02 ............................................... 5 

Cdk /2 Inhibitor III ........................................................ 6, 9 

Cdk /5 Inhibitor ............................................................. 6, 20 

Cdk2 Inhibitor I ...................................................................... 6 

Cdk2 Inhibitor II..................................................................... 6 

Cdk2 Inhibitor III ................................................................... 6 

Cdk2 Inhibitor IV, NU6 40 ................................................. 6 

Cdk2/5 Inhibitor .................................................................... 6 

Cdk2/Cyclin Inhibitory Peptide I ....................................... 6 

Cdk2/Cyclin Inhibitory Peptide II ...................................... 6 

Cdk4 Inhibitor ........................................................................ 6 

Cdk4 Inhibitor II, NSC 625987 .......................................... 6 

Cell Sheet Migration Inhibitor ..........................................70 

Cell Sheet Migration Inhibitor, Negative Control ........70 

Cerulenin, Cephalosporium caerulens ......................88, 89 

cFMS Receptor Tyrosine Kinase Inhibitor .......................48 

CGP-37 57 ........................................................................... 5 

Chelerythrine Chloride .........................................................38 

Chk2 Inhibitor ........................................................................ 2 

Chk2 Inhibitor II .................................................................... 2 

Chloramphenicol ................................................................ 60 

Chlorhexidine, Dihydrochloride ...................................... 20 

Chlorpromazine, Hydrochloride ..................... 95, 0, 57 

Chymostatin ........................................................................ 28 

Chymotrypsin Inhibitor I, Potato ................................... 28 

Cilostamide .......................................................................... 57 

CL-387,785 .............................................................................48 

CL-82 98 .............................................................................. 20 

Clioquinol ................................................................................96 

c-Met Inhibitor (Met Kinase Inhibitor) ...........................53 

CoEnzyme A, Trilithium Salt ...............................................85 

Collagenase Inhibitor I ...................................................... 7 

Collagenase Substrate II ................................................... 7 

Collagenase Substrate III, Fluorogenic .......................... 7 

Compound 52 ......................................................................... 6 

Compound 56 .........................................................................48 

Conduritol B Epoxide ........................................................ 47 

COX- Inhibitor, FR 22047 ................................................86 

COX-2 Inhibitor I ...................................................................86 

COX-2 Inhibitor II..................................................................86 

cPLA2a Inhibitor ...................................................................94 

CrmA, Recombinant.......................................................65, 66 

Cucurbitacin I, Cucumis sativus L. ....................................49 

Curcumin, Curcuma longa L. ................................49, 86, 9 

2-Cyanoethylalsterpaullone ........................................ 5, 9 

4-Cyano-3-methylisoquinoline .........................................34 

Cyclin-Dependent Protein Kinase Inhibitor Set............ 7 

Cycloheximide ..................................................................... 60 

InSolution Cycloheximide ............................................. 60 

Cycloheximide, High Purity ............................................. 60 

Cyclooxygenase Inhibitor Set ............................................88 

Cyclopamine, V. californicum ......................................... 62 

Cyclopamine-KAAD ........................................................... 62 

Cyclopiazonic Acid, Penicillium cyclopium ................ 42 

Cyclosporin A, Tolypocladium inflatum ...........................59 

Cyclo(Arg-Gly-Asp-D-Phe-Val) .........................................70 

Cypermethrin ..........................................................................59 

Cystatin, Egg White ........................................................... 28 

D 

D609 Prodrug .........................................................................93 

D609, Potassium Salt ...........................................................93 

Daidzein ..............................................................................9, 49 

Index 

Damnacanthal ........................................................................49 

,5-Dansyl-Glu-Gly-Arg Chloromethyl Ketone, 

Dihydrochloride ............................................................ 28 

Daphnetin .........................................................................34, 49 

DARPP-32, Phospho-, Rat, Recombinant, E. coli ..........59 

DARPP-32, Rat, Recombinant, E. coli ..............................59 

Daunorubicin, Hydrochloride .............................................82 

Debromohymenialdisine, Stylotella aurantium ............ 2 

(-)-Deguelin, Mundulea sericea .................................5, 5 

Deltamethrin ..........................................................................59 

Denbufylline......................................................................... 57 

2-Deoxy-D-galactose........................................................ 47 

3´-Deoxy-2´,3´-didehydrothymidine ...............................80 

Deoxyfuconojirimycin, Hydrochloride .......................... 47 

Deoxygalactonojirimycin, Hydrochloride..................... 47 

-Deoxymannojirimycin, Hydrochloride ...................... 48 

5´-Deoxy-5´-methylthioadenosine ........................49, 44 

-Deoxynojirimycin, Hydrochloride .............................. 48 

Dephostatin ............................................................................59 

3,4-Dephostatin.....................................................................59 

3,4-Dephostatin, Ethyl- .......................................................59 

Dequalinium Chloride ..........................................................38 

Dexamethasone ................................................................... 0 

3,4-Dichloroisocoumarin ..........................................95, 28 

5,6-Dichloro- -b-D-ribofuranosylbenzimidazole .........9 

Diclofenac Sodium .........................................................86, 96 

Diclofenac, 4'-Hydroxy- ......................................................86 

Dicoumarol ..............................................................................22 

2',5'-Dideoxyadenosine .................................................... 39 

Diethyl Pyrocarbonate .........................................................77 

DL-a-Difluoromethylornithine, Hydrochloride .......... 04 

Diisopropylfluorophosphate .....................................98, 28 

7-DMAG ............................................................................. 49 

N G ,N G -Dimethyl-L-arginine, Dihydrochloride .............. 0 

N G ,N G´ -Dimethyl-L-arginine, Dihydrochloride ............. 0 

Eg5 Inhibitor III, Dimethylenastron ............................... 42 

,4-Dimethylendothall ........................................................60 

Dipeptidylpeptidase II Inhibitor ..................................... 28 

Dipeptidylpeptidase IV Inhibitor I .................................. 28 

Dipeptidylpeptidase IV Inhibitor II ................................ 28 

Diphenyleneiodonium Chloride ....................................... 0 

Dipyridamole ....................................................................... 57 

7-DMAG ............................................................................. 49 

DMBI .........................................................................................49 

DNA Base Excision Repair Pathway Inhibitor ...............77 

DNA Methyltransferase Inhibitor .....................................7 

DNA-PK Inhibitor .................................................................. 8 

DNA-PK Inhibitor II............................................................... 8 

DNA-PK Inhibitor III ............................................................. 8 

DNA-PK Inhibitor IV ............................................................. 8 

DNA-PK Inhibitor V............................................................... 8 

DNase g Inhibitor, 6-DTAF...................................................77 

Doxorubicin, Hydrochloride ................................................83 

DPC ....................................................................................... 42 

DPQ ...........................................................................................79 

Drosophila Antennapedia Homeo-Domain (43-58) ....43 

DuP-697 ...................................................................................86 

E 

E-64 Protease Inhibitor .................................................... 28 

E-64, Immobilized .............................................................. 28 

EB-47 ........................................................................................79 

Ebselen .....................................................................................86 

Ecotin, E. coli ....................................................................... 29 

EDTA, Disodium Salt, Dihydrate, Molecular 

Biology Grade ................................................................ 29 

EDTA, Tetrasodium Salt ..................................................... 29 

Eg5 Inhibitor II .................................................................... 42 

Eg5 Inhibitor III, Dimethylenastron ............................... 42 

EGFR/ErbB-2 Inhibitor .........................................................49 

EGTA ....................................................................................... 29 

EGTA, Molecular Biology Grade ..................................... 29 

EHNA, Hydrochloride......................................................... 57 

Eicosapentaenoic Acid .........................................................92 

eIF-2a Inhibitor, Salubrinal................................................60 

Elastase Inhibitor I .................................................... 8, 29 

Elastase Inhibitor II ................................................... 8, 29 

Elastase Inhibitor III ................................................. 8, 29 

Elastase Inhibitor IV ........................................................... 8 

Elastatinal ............................................................................ 29 

Ellagic Acid, Dihydrate ......................................9, 34, 38, 83 


Phone 800 628 8470 


67

Index 

Ellipticine .................................................................................83 

Ellipticine, 9-Hydroxy-, Hydrochloride ...........................80 

Emetine, Dihydrochloride ................................................. 60 

Emodin .....................................................................................49 

Endothall .................................................................................60 

(–)-Epigallocatechin Gallate .......................................7 , 80 

Epirubicin Hydrochloride.....................................................83 

Epoxomicin, Synthetic ...................................................... 37 

InSolution Epoxomicin, Synthetic .............................. 39 

Erbstatin Analog ....................................................................49 

ERK Activation Inhibitor Peptide I, Cell-Permeable.....25 

ERK Activation Inhibitor Peptide II, Cell-Permeable ...25 

ERK Inhibitor ..........................................................................25 

Erythromycin, Streptomyces erythreus ........................ 60 

EST ................................................................................. 6, 29 

ET- 8-OCH 3 ......................................................................3 , 93 

Etazolate, Hydrochloride .................................................. 57 

N-Ethylmaleimide .............................................................. 42 

2-Ethyl-2-thiopseudourea, Hydrobromide .................. 0 

Etoposide .................................................................................83 

Etoposide Phosphate ............................................................83 

ETYA ...................................................................................86, 92 

Evodiamine, Evodia rutaecarpa ...................................... 54 

F 

F 6 .......................................................................................... 5 

FAAH Inhibitor I .....................................................................88 

FAAH Inhibitor II....................................................................88 

Fas/FasL Antagonist, Kp7-6................................................67 

Fascaplysin, Synthetic .......................................................... 6 

Fatty Acid Synthase Inhibitor, C75...................................88 

Fenvalerate..............................................................................60 

Flurbiprofen .....................................................................86, 96 

Fluvastatin, Sodium Salt .....................................................89 

FMS c Receptor Tyrosine Kinase Inhibitor (cFMS 

Receptor Tyrosine Kinase Inhibitor) ...........................48 

Folimycin, Streptomyces sp. ........................................... 42 

Fostriecin, Sodium Salt, 

Streptomyces pulveraceous .........................................60 

FPT Inhibitor I ...................................................................... 44 

FPT Inhibitor II ..................................................................... 45 

FPT Inhibitor III ................................................................... 45 

FR- ..........................................................................................70 

FTase Inhibitor I .................................................................. 45 

FTase Inhibitor II ................................................................. 45 

FTase Inhibitor III................................................................ 45 

FTI-276 .................................................................................. 45 

FTI-277 .................................................................................. 45 

FTI-2 48 ................................................................................ 45 

FTI-2628 ............................................................................... 45 

Fumonisin B , Fusarium moniliforme ...............................95 

Furin Inhibitor I .................................................................... 8 

Furin Inhibitor II .................................................................. 8 

FUT- 75 ................................................................................ 29 

G 

G 4 8 Sulfate, Cell Culture Tested ................................ 60 

G 4 8 Sulfate, Sterile-Filtered Aqueous Solution, 

Cell Culture Tested ...................................................... 6 

Galanthamine, Hydrobromide ...........................................98 

InnoZyme Gelatinase Activity Assay Kit, 

Fluorogenic .................................................................... 22 

Geldanamycin, Streptomyces hygroscopicus ......49, 49 

Genistein ................................................................... 49, 83, 96 

Genistin ....................................................................................49 

Gentamycin Sulfate ..............................................................95 

GGACK ................................................................................... 29 

GGTI-286 .............................................................................. 45 

GGTI-287 .............................................................................. 46 

GGTI-297 .............................................................................. 46 

GGTI-298 .............................................................................. 46 

GGTI-2 33 ............................................................................ 46 

GGTI-2 47 ............................................................................ 46 

Gliotoxin, Gladiocladiumfimbriatum ................... 46, 54 

H-Gly-Arg-Ala-Asp-Ser-Pro-OH ......................................70 

H-Gly-Arg-Gly-Asp-Ser-OH ...............................................70 

H-Gly-Arg-Gly-Asp-Ser-Pro-OH ......................................70 

H-Gly-Arg-Gly-Asp-Thr-Pro-OH .......................................70 

b-Glycerophosphate, Disodium Salt, Pentahydrate ....60 

GM 489 ............................................................................... 20 

GM 600 ............................................................................... 20 

InSolution GM600 ........................................................ 20 

GM 600 , Negative Control ............................................ 20 

GNF-2 (Bcr-abl Inhibitor) ...................................................48 

Gö 6976 ...................................................................................38 

InSolution Gö 6976 ...........................................................38 

Gö 6983 ...................................................................................38 

Gö 7874, Hydrochloride ...............................................29, 38 

Granzyme B Inhibitor I .................................................65, 66 

Granzyme B Inhibitor II ................................................65, 66 

Granzyme B Inhibitor IV ...............................................65, 66 

Group III Caspase Inhibitor I ..............................................65 

GSK-3b Inhibitor I ................................................................20 

GSK-3b Inhibitor II ...............................................................20 

GSK-3b Inhibitor III ..............................................................20 

GSK-3b Inhibitor VI ..............................................................20 

GSK-3b Inhibitor VII .............................................................20 

GSK-3b Inhibitor VIII ...........................................................20 

InSolution GSK-3b Inhibitor VIII ............................20, 84 

GSK-3b Inhibitor XI ..............................................................20 

GSK-3b Inhibitor XII, TWS 9 ...........................................20 

GSK-3b Peptide Inhibitor ....................................................2 

GSK-3b Peptide Inhibitor, Cell-permeable.....................2 

GSK-3 Inhibitor IX.......................................................... 6, 20 

InSolution GSK-3 Inhibitor IX .................................. 6, 20 

GSK-3 Inhibitor X ..................................................................20 

GSK-3 Inhibitor XIII ..............................................................20 

GSK-3 Inhibitor XIV, Control, MeBIO ..............................20 

GTP- 4564 ..............................................................................49 

2-Guanidinoethylmercaptosuccinic Acid .................... 29 

Guanosine 3´,5´-cyclic Monophosphorothioate, 

8-(4-Choloro-phenylthio)-, Rp-Isomer, 

Triethylammonium Salt .................................................43 


8-Bromo-, Rp-Isomer, Sodium Salt ...........................43 


b-Phenyl- , N2-etheno-8-bromo-, Rp-Isomer, 

Sodium Salt ......................................................................43 


Rp-Isomer, Triethylammonium Salt ...........................43 

H 

H-7, Dihydrochloride ............................................. 34, 38, 44 

Iso-H-7, Dihydrochloride ....................................................38 

H-8, Dihydrochloride ............................................................34 

H-9, Dihydrochloride .....................................................34, 44 

H-9, Immobilized...................................................................44 

H-89, Dihydrochloride ............................................... 7, 9, 34 

InSolution H-89, Dihydrochloride ............................9, 34 

HA 004, Dihydrochloride.......................................7, 34, 44 

HA 077, Dihydrochloride .................................... 34, 44, 56 

Haloperidol ............................................................................ 0 

HBDDE ......................................................................................38 

Hdm2 E3 Ligase Inhibitor ................................................ 37 

HDSF ...................................................................................... 29 

Heat Shock Protein Inhibitor I ........................................ 49 

Heat Shock Protein Inhibitor II ...................................... 49 

Helenalin, A. chamissonis ssp. foliosa ........................... 54 

Herbimycin A, Streptomyces sp. ........................................49 

Hexokinase II VDAC Binding Domain Peptide, 

Cell-Permeable ............................................................. 5 

Hinokitiol .................................................................................92 

Hispidin ....................................................................................38 


Colorimetric ......................................................................75 


Fluorometric .....................................................................75 

Histone Deacetylase HD2, Maize ......................................75 

Histone Deacetylase Inhibitor I .........................................73 

Histone Deacetylase Inhibitor II........................................74 

Histone Deacetylase Inhibitor III ......................................74 

N Histone Deacetylase, Human, 

Recombinant, S. frugiperda..........................................75 

Histone Deacetylase, Rat Liver ..........................................75 

HIV Protease Inhibitor ...................................................... 29 

HNMPA-(AM) 3 ........................................................................49 

Hsp25 Kinase Inhibitor ..............................................25, 49 

Hsp27 ELISA Kit .................................................................. 49 

HSV Replication Inhibitor, BP5 ..........................................72 

Humanin, Human, Synthetic ..............................................67 

(–)-Huperzine A, Huperzia serrata ...................................98 

(±)-Huperzine A .....................................................................98 

N G -Hydroxy-L-arginine, Monoacetate Salt ................ 04 

N w -Hydroxy-nor-L-arginine, Diacetate Salt ............... 04 

a-Hydroxyfarnesylphosphonic Acid ............................. 46 

Hydroxyfasudil .......................................................................56 

4-Hydroxynonenal ............................................................. 42 

Hygromycin B, Streptomyces sp. .................................... 6 

Hymenialdisine, Stylissa damicornis .................. 6, 2 , 26 

Hypericin........................................................................... 0, 38 

Hypocrellin B, Hypocrella bambusae ........................... 43 

Hypoestoxide, Hypoestes rosea ...................................... 54 

I 

IkB Kinase Inactive Control Peptide, 


IkB Kinase Inhibitor Peptide, Cell-Permeable ............ 54 

(±)-Ibuprofen ..........................................................................87 

IC26 ........................................................................................ 0 

ICG .............................................................................................2 

IGF- R Inhibitor, PPP ...........................................................49 

IKK Inhibitor II, Wedelolactone ...................................... 54 

IKK Inhibitor III, BMS-34554 ........................................ 55 

IKK-2 Inhibitor IV ............................................................... 55 

IKK-2 Inhibitor V ................................................................ 55 

IKK-2 Inhibitor VI ............................................................... 55 

IKK-2 Inhibitor, SC-5 4 .................................................... 55 

InSolution IKK-2 Inhibitor, SC-5 4 ............................ 55 

L-N 5 -( -Iminoethyl)ornithine, Dihydrochloride .......... 0 

Indirubin Derivative E804 ................................................... 7 

Indirubin-3´-monoxime ............................................... 7, 2 

Indirubin-3´-monoxime, 5-Iodo- .............................. 7, 2 

Indirubin-3´-monoxime-5-sulphonic Acid ............. 7, 2 

Indomethacin .........................................................................87 

Indomethacin Amide, N-Octyl- .........................................87 

Indomethacin Ester, 4-Methoxyphenyl- .........................87 

Indomethacin Ester, n-Heptyl- ..........................................87 

InnoZyme Gelatinase Activity Assay Kit, 

Fluorogenic .................................................................... 22 

InnoZyme TACE Activity Kit ......................................... 03 

InSolution AG 478 ...........................................................48 

InSolution Akt Inhibitor IV ................................................4 

InSolution Akt Inhibitor VIII, Isozyme-Selective, 

Akti- /2 ...............................................................................4 

InSolution ALLN ...................................................... 5, 25 

InSolution AMPK Inhibitor, Compound C ...............5, 84 

InSolution AZT, Triphosphate,Tetralithium Salt .........80 

InSolution BAY -7082 ................................................ 54 

InSolution Bisindolylmaleimide I ...................................37 

InSolution Blebbistatin, Racemic ................................ 42 

InSolution Casein Kinase II Inhibitor, DMAT..........9, 84 


InSolution Casein Kinase I Inhibitor, D4476..........9, 84 

InSolution Caspase-3 Inhibitor I, Cell-Permeable ....64 

InSolution Caspase-3 Inhibitor II ..................................64 

InSolution Caspase-8 Inhibitor II ...........................65, 66 

InSolution Caspase-9 Inhibitor I ....................................65 

InSolution Caspase Inhibitor I ........................................64 

InSolution Caspase Inhibitor VI......................................64 

InSolution Cycloheximide ............................................. 60 

InSolution Epoxomicin, Synthetic .............................. 37 

InSolution GM600 ........................................................ 20 

InSolution Gö 6976 ...........................................................38 

InSolution GSK-3 Inhibitor IX .................................. 6, 20 

InSolution GSK-3b Inhibitor VIII ............................20, 84 

InSolution H-89, Dihydrochloride ............................9, 34 

InSolution IKK-2 Inhibitor, SC-5 4 ............................ 55 

InSolution JAK Inhibitor I .........................................50, 84 

InSolution JNK Inhibitor II ...............................................22 


Nocardiopsis sp. ................................... 7, 29, 34, 38, 44 

InSolution KN-93 .................................................................7 

InSolution KT5720 .............................................................34 

InSolution Leptomycin A, Streptomyces sp. ...............76 

InSolution Leptomycin B, Streptomyces sp. ...............76 

InSolution LY 294002 .......................................................3 

InSolution MANT-GppNHp ........................................... 40 

InSolution MANT-GTPgS ............................................... 40 

InSolution MG- 32 ........................................................ 37 

68 Orders Phone 800 854 34 7 


Fax 800 776 0999 


InSolution Microcystin-LR, 

Microcystis aeruginosa.................................................60 

InSolution ML 3 63 ...........................................................26 

InSolution NF-kB Activation Inhibitor...................... 55 

InSolution Okadaic Acid, 

Prorocentrum concavum ...............................................60 

InSolution Olomoucine ..................................................... 7 

InSolution OM99-2 ......................................................... 0 

InSolution p38 MAP Kinase Inhibitor III ...............26, 84 

InSolution PD 53035 ......................................................5 

InSolution PD 58780 ......................................................84 

InSolution PP2 ....................................................................5 

InSolution Proteasome Inhibitor I .............................. 38 

InSolution Q-VD-OPh, Non-O-methylated .................65 

InSolution Raf Kinase Inhibitor I .................................55 

InSolution Rapamycin .......................................................84 

InSolution Ratjadone A, Synthetic ................................77 

InSolution Rho Kinase Inhibitor ..............................56, 84 

InSolution Ro-3 -8220 ....................................................40 

InSolution Roscovitine ...................................................... 7 

InSolution SB 202 90 .......................................................26 

InSolution SB 203580 .......................................................27 

InSolution g-Secretase Inhibitor IX ............................. 02 

InSolution g-Secretase Inhibitor X .............................. 02 

InSolution g-Secretase Inhibitor XIX ......................... 03 

InSolution g-Secretase Inhibitor XVII ......................... 02 

InSolution Sinefungin .......................................................7 

InSolution Sirtinol ..............................................................74 

InSolution Staurosporine, Streptomyces sp................35 

InSolution SU6656.............................................................52 

InSolution TAPI- ............................................................. 7 

InSolution Tautomycetin, S. griseochromogenes ......62 

InSolution Trichostatin A, Streptomyces sp................74 

InSolution VEGF Receptor 2 Kinase Inhibitor III......53, 84 

InSolution Y-27632 ...........................................................57 

a-Iodoacetamide ............................................................... 29 

5-Iodo-6-amino- ,2-benzopyrone ..................................79 

5-Iodotubercidin ...................................................................26 

I-OMe-AG 538 .......................................................................47 

IP3K Inhibitor .........................................................................23 

3-Isobutyl- -methylxanthine ......................................... 58 

Isogranulatimide ................................................................... 2 

Isohelenin, Inula sp. .......................................................... 55 

,5-Isoquinolinediol .............................................................79 

Isotetrandrine .........................................................................93 

ITSA .........................................................................................74 

J 

JAK Inhibitor I ........................................................................50 

InSolution JAK Inhibitor I .........................................50, 84 

JAK2 Inhibitor II .....................................................................50 

JAK3 Inhibitor I ......................................................................50 

JAK3 Inhibitor II .....................................................................50 

JAK3 Inhibitor III ...................................................................50 

JAK3 Inhibitor IV ...................................................................50 

JAK3 Inhibitor V .....................................................................50 

JAK3 Inhibitor VI ...................................................................50 

JAK3 Inhibitor, Negative Control ......................................50 

Jervine ................................................................................... 62 

JNK Inhibitor I, (L)-Form, Cell-Permeable ......................22 

JNK Inhibitor I, (L)-Form, Cell-Permeable, 

Negative Control .............................................................22 

JNK Inhibitor II .......................................................................22 

InSolution JNK Inhibitor II ...............................................22 

JNK Inhibitor II, Negative Control ....................................22 

JNK Inhibitor III, Cell-Permeable ......................................22 

JNK Inhibitor III, Cell-Permeable, Negative Control ....23 

JNK Inhibitor V .......................................................................23 

K 

K-252a, Nocardiopsis sp. ......................... 7, 29, 34, 38, 44 


Nocardiopsis sp. ................................... 7, 29, 34, 38, 44 

K-252b, Nocardiopsis sp. .............................. 29, 34, 38, 44 

K-252c ......................................................................................38 

Kaempferol ..............................................................................87 

Kanamycin Sulfate, Streptomyces kanamyceticus ... 6 

Kanamycin Sulfate, Streptomyces kanamyceticus, 

Cell Culture-Tested ...................................................... 6 


Kenpaullone ..................................................................... 7, 2 

Ketoconazole ..........................................................................92 

(Z-LL) 2 Ketone...................................................................... 29 

Kifunensine, Kitasatosporia kifunense ......................... 48 


Single Chain, Human Plasma ................................... 30 


Two Chain, Human Plasma........................................ 30 

Kininogen, Low Molecular Weight, 

Human Plasma .............................................................. 30 

KN-62 .........................................................................................7 

KN-92 .........................................................................................7 

KN-93 .........................................................................................7 

InSolution KN-93 .................................................................7 

KN-93, Water-Soluble ...........................................................7 

KT5720 .....................................................................................34 

InSolution KT5720 .............................................................34 

KT5823 .....................................................................................44 

L 

L-744,832 ............................................................................. 46 

Lactacystin, Synthetic ....................................................... 37 

clasto-Lactacystin-b-lactone ........................................ 37 

Lavendustin A .........................................................................50 

Lavendustin B .........................................................................50 

Lavendustin C ....................................................................8, 50 

Lck Inhibitor ............................................................................50 

InSolution Leptomycin A, Streptomyces sp. ...............78 

InSolution Leptomycin B, Streptomyces sp. ...............78 

Leuhistin ............................................................................... 30 

Leupeptin, Hemisulfate .................................................... 30 

LFM-A ...................................................................................50 

LFM-A 2 ..................................................................................50 

LFM-A 3 ..................................................................................50 

Lipase Inhibitor, THL .............................................................90 

Lipase Inhibitor, URB602, Monoacylglycerol 

(Monoacylglycerol Lipase Inhibitor, URB602) .........90 

Lovastatin ................................................................................89 

Lovastatin, Sodium Salt.......................................................89 

Luteolin ................................................................................. 05 

LY 83583 ............................................................................... 06 

LY 294002 ...............................................................................3 

InSolution LY 294002 .......................................................3 

LY 3035 ................................................................................3 

M 

a 2 -Macroglobulin, Human Plasma................................ 30 

Mannostatin A, Hydrochloride ....................................... 48 

InSolution MANT-GppNHp ........................................... 40 

InSolution MANT-GTPgS ............................................... 40 

Manumycin A, Streptomyces parvulus ..................95, 46 

MAP Kinase Cascade Inhibitor Set ...................................28 

MAP Kinase Inhibitor Set I .................................................28 

MAP Kinase Inhibitor Set II ................................................28 

Mastoparan .......................................................................... 43 

MDL- 2,330A, Hydrochloride ......................................... 40 

MEG, Hydrochloride............................................................ 0 

MEK Inhibitor I .......................................................................26 

MEK Inhibitor II .....................................................................26 

MEK Inhibitor Set ..................................................................28 

MEK /2 Inhibitor ...................................................................26 

Melatonin .............................................................................. 0 

Melittin ..........................................................................38, 40 

Meloxicam ...............................................................................87 

Merbarone ...............................................................................83 

DL-2-Mercaptomethyl-3- 

guanidinoethylthiopropanoic Acid ......................... 30 

Met Kinase Inhibitor ............................................................50 

8-Methoxymethyl-3-isobutyl- -methylxanthine .... 58 

Methyl Arachidonyl Fluorophosphonate ........................93 

Methylene Blue ................................................................... 06 

4-{[3´,4´-(Methylenedioxy)benzyl]amino} 

-6-methoxyquinazoline ............................................. 58 

S-Methylisothiourea, Sulfate .......................................... 0 

S-Methyl-L-thiocitrulline, Dihydrochloride ................. 0 

a-Methylomuralide ........................................................... 37 

Mevastatin ..............................................................................89 

Mevastatin, Sodium Salt .....................................................89 

MG- 5 ................................................................................ 37 

Index 

MG- 32 ....................................................................... 0 , 37 

InSolution MG- 32 ........................................................ 39 

Microcystin-LF, Microcystis aeruginosa .........................60 

Microcystin-LR, Microcystis aeruginosa .........................60 

InSolution Microcystin-LR, 

Microcystis aeruginosa.................................................60 

Microcystin-LW, Microcystis aeruginosa ........................60 

Microcystin-RR, Microcystis aeruginosa ........................60 

MIF Antagonist, ISO- ...................................................... 63 

Milrinone .............................................................................. 58 

Mitochondrial Permeability Transition 

Pore Reagents Set ........................................................ 52 

MJ33 .........................................................................................94 

MK-886 ....................................................................................92 

MK2a Inhibitor .......................................................................26 

InSolution ML 3 63 ...........................................................26 

ML-7, Hydrochloride ............................................................29 

ML-9, Hydrochloride ............................................................29 

MMP Inhibitor I .................................................................. 20 

MMP Inhibitor II ................................................................. 20 

MMP Inhibitor III ................................................................ 20 

MMP Inhibitor IV ................................................................ 20 

MMP- ELISA Kit .............................................................. 22 

MMP-2 ELISA Kit .............................................................. 22 

MMP-2 Inhibitor I .............................................................. 20 

MMP-2 Inhibitor II ............................................................ 20 

MMP-2/MMP-3 Inhibitor I .............................................. 2 

MMP-2/MMP-3 Inhibitor II ............................................ 2 

MMP-2/MMP-9 Inhibitor I .............................................. 2 

MMP-2/MMP-9 Inhibitor II ............................................ 2 

MMP-2/MMP-9 Inhibitor III ........................................... 2 

MMP-2/MMP-9 Inhibitor IV ........................................... 2 

MMP-2/MMP-9 Inhibitor V ............................................ 2 

MMP-3 ELISA Kit ............................................................... 22 


MMP-3 Inhibitor II ............................................................ 2 

MMP-3 Inhibitor III ........................................................... 2 

MMP-3 Inhibitor IV ........................................................... 2 

MMP-3 Inhibitor V ............................................................ 2 

MMP-3 Inhibitor VI ........................................................... 2 

MMP-3 Inhibitor VII .......................................................... 2 

MMP-3 Inhibitor VIII ......................................................... 2 


MMP-8 Inhibitor I, Negative Control ........................... 2 

MMP-9 ELISA Kit .............................................................. 22 


MMP-9/MMP- 3 Inhibitor I ........................................... 22 

MMP-9/MMP- 3 Inhibitor II .......................................... 22 

Active MMP- 3 ELISA Kit ................................................ 22 

MMP- 3 Inhibitor .............................................................. 22 

Monoacylglycerol Lipase Inhibitor, URB602 ..................90 

N G -Monoethyl-L-arginine, Monoacetate Salt ............ 0 

N G -Monomethyl-D-arginine, Monoacetate Salt ........ 0 

N G -Monomethyl-L-arginine, Monoacetate Salt ......... 

mpV(pic) ...................................................................................60 

MY-5445 ............................................................................... 58 

Mycalolide B, Mycale sp. ................................................. 43 

Myosin Light Chain Kinase Inhibitor Peptide 8 ..........29 

N 

Naltrindole, Hydrochloride ...................................................5 

a-Naphthyl Acid Phosphate, Monosodium Salt ..........60 

NC- 300-B .......................................................................... 43 

NDGA, Larrea divaricata ......................................................92 

Necrosis Inhibitor, IM-54 ....................................................68 

Necrostatin- .........................................................................68 

Necrostatin- , Inactive Control ........................................68 

NEMO-Binding Domain Binding Peptide, 


NEMO-Binding Domain Binding Peptide, 

Cell-Permeable, Negative Control ........................... 55 

Neomycin Sulfate ..................................................................94 

Neomycin Sulfate, g-Irradiated, 

Tissue Culture Grade ......................................................94 

NFAT Activation Inhibitor III ..............................................60 

NF-kB Activation Inhibitor.............................................. 55 

InSolution NF-kB Activation Inhibitor...................... 55 

NF-kB SN50, Cell-Permeable Inhibitor Peptide ........ 56 

NF-kB SN50M, Cell-Permeable Inactive 

Control Peptide ............................................................. 56 


Phone 800 628 8470 


69

Index 

NF-kB Activation Inhibitor II, JSH-23 ......................... 56 

NGIC-I ......................................................................................39 

Niflumic Acid ...................................................................87, 97 

L-NIL, Dihydrochloride ....................................................... 

NIPP- , His•Tag ® , Bovine Thymus, 

Recombinant, E. coli .......................................................60 

Nitric Oxide Assay Kit, Colorimetric .............................. 2 

Nitric Oxide Assay Kit, Fluorometric .............................. 2 

Nitric Oxide Synthase Assay Kit ...................................... 2 

Nitric Oxide Synthase Assay Kit, Colorimetric ............ 2 

Nitric Oxide Synthase, Inducible, Inhibitor Set .......... 2 

p-Nitroblue Tetrazolium Chloride................................... 

7-Nitroindazole ................................................................... 

7-Nitroindazole, 3-Bromo-, Sodium Salt ..................... 

7-Nitroindazole, Sodium Salt .......................................... 

N G -Nitro-L-arginine ........................................................... 

N G -Nitro-L-arginine Methyl Ester, Hydrochloride ..... 

5-Nitro-2-(3-phenylpropyl-amino)benzoic Acid .........87 

NLVS ....................................................................................... 37 

nNOS Inhibitor I................................................................... 

NOS Inhibitor Set ................................................................ 2 

Novobiocin, Sodium Salt .....................................................72 

NP-LLL-VS ............................................................................ 37 

NPPB ..................................................................................23, 26 

NS-398 .....................................................................................87 

NS 2028 ................................................................................ 06 

N-SMase Inhibitor, GW4869 .............................................93 

NU 025 ....................................................................................79 

O 

ODQ ........................................................................................ 06 

Okadaic Acid, Ammonium Salt ..........................................60 

Okadaic Acid, Potassium Salt ............................................6 

Okadaic Acid, Prorocentrum concavum ..........................60 

InSolution Okadaic Acid, 

Prorocentrum concavum ...............................................60 

Okadaic Acid, Sodium Salt .................................................6 

Oligomycin .................................................................. 43, 5 

Olomoucine ............................................................................. 7 

InSolution Olomoucine ..................................................... 7 

Olomoucine II ......................................................................... 7 

Olomoucine, Iso- ................................................................... 7 

Olomoucine, N 9 -Isopropyl- ................................................. 7 

InSolution OM99-2 ......................................................... 0 

Omeprazole .......................................................................... 43 

Omi/HtrA2 Protease Inhibitor, Ucf- 0 ..........................67 

Oridonin, R. rubescens ...................................................... 56 

Ouabain, Octahydrate ....................................................... 43 

Oxamflatin ..............................................................................74 

Oxindole I ................................................................................5 

P 

p38 MAP Kinase Inhibitor ...................................................26 

p38 MAP Kinase Inhibitor III ..............................................26 

InSolution p38 MAP Kinase Inhibitor III ...............26, 84 

p-APMSF, Hydrochloride .................................................. 26 

PACOCF 3 ...................................................................................94 

PARP Cleavage Detection Kit .............................................79 

PARP Inhibitor Set ................................................................79 

Parthenolide, Tanacetum parthenium .......................... 56 

,3-PBITU, Dihydrobromide .............................................. 

PD 98059 .................................................................................26 

PD 45305 ............................................................................ 6 

PD 50606 ............................................................................ 6 

PD 5 746 ............................................................................. 6 

PD 53035 ..............................................................................5 

InSolution PD 53035 ......................................................5 

PD 56273 ..............................................................................5 

PD 58780 ..............................................................................5 

InSolution PD 58780 ......................................................84 

PD 68393 ..............................................................................5 

PD 693 6 ...............................................................................26 

PD 74265 ..............................................................................5 

PDGF Receptor Tyrosine Kinase Inhibitor I ....................5 

PDGF Receptor Tyrosine Kinase Inhibitor II ...................5 

PDGF Receptor Tyrosine Kinase Inhibitor III ..................5 

DL-threo-PDMP, Hydrochloride...................................... 48 

a -PDX, Human, Recombinant, E. coli ......................... 30 

Pentoxifylline ..........................................................................70 

Pepstatin A Methyl Ester .................................................. 0 

Pepstatin A, Synthetic....................................................... 30 

Pfmrk Inhibitor, WR 2 6 74 .............................................. 7 

Phenylarsine Oxide ...............................................................6 

Phenylmethylsulfonyl Fluoride ...................................... 30 

Phloretin ..................................................................................39 

PHM-L LIPOSORB Absorbent ..........................................90 

Phorbol- 2, 3-dibutyrate ............................................... 43 

Phosphatase Inhibitor Cocktail Set I ...............................62 

Phosphatase Inhibitor Cocktail Set II ..............................62 

Phosphatase Inhibitor Cocktail Set III .............................62 

Phosphatase Inhibitor Cocktail Set IV .............................62 

5-Phosphatase Inhibitor .....................................................6 

Phosphodiesterase 4 Inhibitor ........................................ 58 

Phosphodiesterase Inhibitor Set I .................................. 58 

Phosphodiesterase V Inhibitor II .................................... 58 

Phosphoramidon, Disodium Salt .................................... 30 

Phosphotyrosine Phosphatase Inhibitor Set 

(Vanadium) .......................................................................62 

PI 3-Kg Inhibitor ....................................................................3 

PI 3-Kg Inhibitor II ................................................................32 

Piceatannol ....................................................... 29, 34, 39, 5 

Pifithrin-a ...............................................................................67 

Pifithrin-a, Cyclic-................................................................67 

PIPER .........................................................................................80 

PJ34 ...........................................................................................79 

PKC b Inhibitor .........................................................................39 

PKC bII /EGFR Inhibitor ............................................................39 

PKC i , GST-Fusion Protein, Active, Human, 


PKC m , GST-Fusion Protein, Active, Human, 


PKC n , GST-Fusion Protein, Active, Human, 


Plasminogen Activator Inhibitor- , Human, 

Recombinant ................................................................. 59 

Plasminogen Activator Inhibitor- , Mutant, 

Human, Recombinant ................................................. 59 

Plasminogen Activator Inhibitor- , Mutant, 

Mouse, Recombinant .................................................. 59 

Plasminogen Activator Inhibitor- , Rat, 

Recombinant ................................................................. 59 

Polymyxin B Sulfate .............................................................39 

PP Analog ..............................................................................5 

PP Analog II, NM-PP ................................................8, 5 

PP2 ............................................................................................5 

InSolution PP2 ....................................................................5 

PP3 ............................................................................................5 

PPACK II, Trifluoroacetate Salt ....................................... 30 

PPACK, Dihydrochloride .................................................... 30 

PPACK Dihydrochloride, Biotinylated ........................... 30 

PPM- 8 ......................................................................... , 56 

Pravastatin, Sodium Salt .....................................................89 

Prolyl Endopeptidase Inhibitor II ................................... 3 

N G -Propyl-L-arginine ......................................................... 

Protease Arrest Reagent ................................................ 34 

Protease Inhibitor Cocktail Set I .................................... 32 

Protease Inhibitor Cocktail Set I, Animal-Free .......... 35 

Protease Inhibitor Cocktail Set II ................................... 32 

Protease Inhibitor Cocktail Set III ................................. 32 

Protease Inhibitor Cocktail Set III, Animal-Free ........ 35 

Protease Inhibitor Cocktail Set IV ................................. 33 

Protease Inhibitor Cocktail Set V, Animal-Free ......... 35 

Protease Inhibitor Cocktail Set V, EDTA-Free ............. 33 

Protease Inhibitor Cocktail Set VI ................................. 33 

Protease Inhibitor Cocktail Set VII ................................ 34 

Protease Inhibitor Cocktail Set VIII ............................... 34 

Protease Inhibitor III, Anthrax Lethal Factor 

(Anthrax Lethal Factor Protease Inhibitor III) ....... 3 

Protease Inhibitor Set ....................................................... 34 

Proteasome Inhibitor I ..................................................... 37 

InSolution Proteasome Inhibitor I .............................. 38 

Proteasome Inhibitor II ..................................................... 38 

Proteasome Inhibitor III ................................................... 38 

Proteasome Inhibitor IV ................................................... 38 

Proteasome Inhibitor VII, Antiprotealide ..................... 38 

Proteasome Inhibitor Set I ............................................... 38 

Proteasome Inhibitor Set II ............................................. 38 

Protein Arginine N-Methyltransferase 

Inhibitor, AMI- ................................................... 46, 60 

Protein Kinase A Inhibitor 5-24 ........................................35 

Protein Kinase A Inhibitor 6-22 Amide...........................35 

Protein Kinase A Inhibitor 4-22 Amide, 

Cell-Permeable, Myristoylated ....................................35 

Protein Kinase C Inhibitor 20-28, 

Cell-Permeable, Myristoylated ....................................39 

Protein Kinase C Inhibitor Peptide 9-3 ......................39 

Protein Kinase C Inhibitor Peptide 9-36 ......................39 

Protein Kinase C Inhibitor Set ...........................................42 

Protein Kinase C Inhibitor, EGF-R Fragment 

65 -658, Myristoylated ................................................39 

Protein Kinase C , His•Tag®, Human, 

a 



bII 

Recombinant ....................................................................42 


d 


Protein Kinase C Translocation Inhibitor Peptide .......40 

e 

Protein Kinase C Translocation Inhibitor Peptide, 

e 

Negative Control .............................................................40 

Protein Kinase C Pseudosubstrate Inhibitor .................39 

z 

Protein Kinase C Pseudosubstrate Inhibitor, 

z 

Myristoylated ...................................................................39 


x 



h 


Protein Kinase C Pseudosubstrate Inhibitor .................39 

θ 


θ 


Protein Kinase C , His•Tag®, 

θ 

Human, Recombinant, S. frugiperda .........................42 

Protein Kinase G Ia Inhibitor, Cell-Permeable ..............44 

Protein Kinase G Inhibitor ..................................................44 

Protein Kinase Inhibitor, DMAP .........................................23 

Protein Phosphatase 2A Inhibitor I PP2A , 

Human Kidney, Recombinant, E. coli .........................6 

Protein Phosphatase 2A Inhibitor I 2 

70 Orders Phone 800 854 34 7 


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PP2A , 

Human, Recombinant, E. coli .......................................6 

Protein Phosphatase Inhibitor 2, Human, 


Protein Phosphatase Inhibitor 2, Rabbit Muscle, 


Protein Phosphatase Inhibitor Set II ................................62 

Protein Synthesis Initiation Inhibitor, 

NSC 9889 .......................................................... 60, 6 

Protein Tyrosine Phosphatase CD45 Inhibitor...............6 

Protein Tyrosine Phosphatase Inhibitor I ........................6 

Protein Tyrosine Phosphatase Inhibitor II ......................6 

Protein Tyrosine Phosphatase Inhibitor III .....................6 

Protein Tyrosine Phosphatase Inhibitor IV .....................6 

P-Selectin Antagonist ..........................................................70 

Pterostilbene, Pterocarpus marsupium ...........................87 

PTP B Inhibitor ......................................................................6 

Puromycin, Dihydrochloride ............................................ 6 

Puromycin, Dihydrochloride, Cell Culture-Tested ..... 6 

Purvalanol A ........................................................................... 7 

-Pyrrolidinecarbodithioic Acid, Ammonium Salt ..... 

Q 

Quercetin, Dihydrate .....................................................32, 94 

Quinacrine, Dihydrochloride .......................................94, 98 

InSolution Q-VD-OPh, Non-O-methylated .................65 

R 

Radicicol, Diheterospora chlamydosporia ...............52, 87 

Raf Kinase Inhibitor I .........................................................55 

InSolution Raf Kinase Inhibitor I .................................55 

InSolution Rapamycin .......................................................84 

InSolution Ratjadone A, Synthetic ................................77 

Resveratrol .......................................................................87, 97 

RG- 3022 ................................................................................52 

Rho-Kinase Inhibitor ............................................................56 

InSolution Rho Kinase Inhibitor ..............................56, 84 

Rho-Kinase Inhibitor II ........................................................56 

Rho-Kinase Inhibitor III, Rockout .....................................56 

Rho Kinase Inhibitor IV ........................................................56 

Ribonuclease Inhibitor, Human, 


Ribonuclease Inhibitor, Human Placenta .......................77 

Rifampicin ...............................................................................72 

RK-682, Streptomyces sp. ...................................................6

RNA Polymerase III Inhibitor ..............................................72 

Ro 06-9920 ..................................................................92, 38 

Ro 06-9920, Control ........................................................ 38 

Ro-20- 724 ......................................................................... 58 

Ro-3 -7549 ............................................................................40 

Ro 3 -7549, Immobilized ...................................................40 

Ro-3 -8220 .....................................................................2 , 40 

InSolution Ro-3 -8220 ....................................................40 

Ro-3 -8425 ............................................................................40 

Ro-32-0432 ............................................................................40 

Rolipram ............................................................................... 58 

Roscovitine .............................................................................. 7 

InSolution Roscovitine ...................................................... 7 

Roscovitine, (S)-Isomer ....................................................... 7 

Rotenone .............................................................................. 5 

Rottlerin ...................................................................................40 

Ru360 .................................................................................... 52 

S 

Safingol ....................................................................................40 

Sangivamycin .........................................................................40 

SANT- .................................................................................. 63 

SB 202 90 ...............................................................................26 

InSolution SB 202 90 .......................................................26 

SB 202 90, Immobilized .....................................................26 

SB 202474 ...............................................................................27 

SB 202474, Dihydrochloride ..............................................27 

SB 203580 ...............................................................................27 

InSolution SB 203580 .......................................................27 

SB 203580, Iodo- ..................................................................27 

SB 203580, Sulfone ..............................................................27 

SB 2 8078 ............................................................................... 2 

SB 220025 ...............................................................................27 

SB 239063 ...............................................................................27 

SBHA .........................................................................................74 

SC-560 .....................................................................................87 

SC-68376 ................................................................................27 

Scriptaid ...................................................................................74 

Scytonemin, Lyngbya sp. .............................................. 2, 4 

b-Secretase Inhibitor II ..................................................... 0 

b-Secretase Inhibitor III .................................................... 0 

b-Secretase Inhibitor IV .................................................... 0 

g-Secretase Inhibitor I ....................................................... 0 

g-Secretase Inhibitor II ...................................................... 0 

g-Secretase Inhibitor III..................................................... 0 

g-Secretase Inhibitor IV..................................................... 0 

g-Secretase Inhibitor V ...................................................... 0 

g-Secretase Inhibitor VI..................................................... 0 

g-Secretase Inhibitor VII ................................................... 02 

g-Secretase Inhibitor IX..................................................... 02 

InSolution g-Secretase Inhibitor IX ............................. 02 

InSolution g-Secretase Inhibitor X .............................. 02 

g-Secretase Inhibitor XI..................................................... 02 

g-Secretase Inhibitor XII ................................................... 02 

g-Secretase Inhibitor XIII .................................................. 02 

g-Secretase Inhibitor XIV .................................................. 02 

g-Secretase Inhibitor XVI .................................................. 02 

InSolution g-Secretase Inhibitor XVII ......................... 02 

InSolution g-Secretase Inhibitor XIX ......................... 03 

g-Secretase Inhibitor XX .................................................. 03 

g-Secretase Inhibitor XXI ................................................. 03 

g 40 -Secretase Inhibitor I ................................................... 03 

g 40 -Secretase Inhibitor II .................................................. 03 

Serine Protease Inhibitor Cocktail Set I ....................... 34 

Serine/Threonine Kinase Inhibitor Set .............................42 

SFK ....................................................................................... 52 

Simvastatin .............................................................................89 

Simvastatin, Sodium Salt ....................................................89 

InSolution Sinefungin .......................................................7 

Sirtinol ......................................................................................74 

InSolution Sirtinol ..............................................................74 

SKF-525A, Hydrochloride.................................................. 

SKF-86002 ............................................................... 27, 87, 92 

Sodium Orthovanadate........................................................6 

Sodium Salicylate..................................................................87 

Sodium Stibogluconate .......................................................62 

Spectinomycin, Dihydrochloride, Pentahydrate, 

Streptomyces sp. .......................................................... 6 

Spermine, Tetrahydrochloride ............................................94 


Sphingosine Kinase Inhibitor .............................................57 

D-erythro-Sphingosine, Dihydro- ..............................4 , 94 

D-erythro-Sphingosine, N,N-Dimethyl- ..................4 , 57 

D-erythro-Sphingosine, Free Base, Bovine Brain .........40 

D-erythro-Sphingosine, Free Base, High Purity ............40 

sPLA 2 -IIA Inhibitor I ..............................................................94 

Spleen Tyrosine Kinase Inhibitor (Syk Inhibitor) ..........52 

Spleen Tyrosine Kinase Inhibitor II (Syk Inhibitor II) ...52 

Splitomicin ..............................................................................74 

SQ 22536 .............................................................................. 40 

Src Family Protein Tyrosine Kinase Inhibitor Set .........54 

Src Kinase Inhibitor I ............................................................52 

Src Kinase Inhibitor II ..........................................................52 

ST638 .................................................................................52, 94 

Staurosporine, Streptomyces sp. ................. 29, 35, 4 , 44 

InSolution Staurosporine, Streptomyces sp................35 

Stem Cell Proliferation Inhibitor .................................... 63 

STO-609 ................................................................................ 5, 8 

Streptomycin Sulfate, Streptomyces sp. ...................... 6 

SU 498.....................................................................................52 

SU4984.....................................................................................52 

SU5402 .....................................................................................52 

SU56 4 .....................................................................................52 

SU6656.....................................................................................52 

InSolution SU6656.............................................................52 

SU95 6 ..................................................................................... 7 

SU 652 ...................................................................................52 

Sulfasalazine .............................................................. 05, 56 

Sulindac ...................................................................................88 

Sulindac Sulfide .....................................................................88 

Sulindac Sulfone ...................................................................88 

Suramin, Sodium Salt .........................................62, 83, 43 

Swainsonine, Swainsona canescens ............................. 48 

Syk Inhibitor ...........................................................................52 

Syk Inhibitor II........................................................................52 

T 

InnoZyme TACE Activity Kit ......................................... 03 

Tamoxifen Citrate..................................................................4 

Tamoxifen, 4-Hydroxy-, (Z)- ..............................................4 

TAPI-0 ..................................................................................... 7 

TAPI- ..................................................................................... 7 

InSolution TAPI- ............................................................. 7 

TAPI-2 .................................................................................... 4 

Tautomycin, Streptomyces spiroverticillatus .................62 

InSolution Tautomycetin, S. griseochromogenes ......62 

Telomerase Inhibitor III, Negative Control, 

Sodium Salt ......................................................................8 

Telomerase Inhibitor III, Sodium Salt ..............................8 

Telomerase Inhibitor VI, Sodium Salt ..............................8 

Telomerase Inhibitor IX........................................................8 

TER 4687 ................................................................................4 

(-)-Terreic Acid, Synthetic ..................................................53 

Tetracycline, Hydrochloride ............................................. 6 

Tetracycline, Hydrochloride, Cell Culture-Tested ...... 6 

Tetrahydrolipstatin (Lipase Inhibitor, THL) .....................90 

TGF-b RI Kinase Inhibitor ............................................53, 57 

TGF-b RI Kinase Inhibitor II .........................................53, 57 

Thapsigargin ........................................................................ 43 

2´-Thioadenosine ..................................................................53 

L-Thiocitrulline, Dihydrochloride .................................... 

DL-Thiorphan .............................................................. 22, 4 

Thiostrepton ......................................................................... 6 

TIMP- ELISA Kit ............................................................... 24 

TIMP- , Human Neutrophil Granulocyte .................... 23 

TIMP- , Recombinant, Bovine ........................................ 23 

TIMP- , Recombinant, Human ....................................... 23 

TIMP-2 ELISA Kit ................................................................ 24 

TIMP-2, Human Rheumatoid Synovial Fibroblast ..... 23 

TIMP-2, Human, Recombinant ....................................... 23 

TIMP-2, Mouse, Recombinant ........................................ 23 

TIMP-3, Human, Recombinant ....................................... 23 

TIMP-3, Mouse Recombinant ......................................... 24 

TIMP-4, Human Fibroblast .............................................. 24 

TIQ-A .........................................................................................79 

TIRAP Inhibitor Peptide, Cell-Permeable ..................... 56 

TIRAP Inhibitor Peptide, Control, Cell-Permeable ..... 56 

TLCK, Hydrochloride .......................................................... 3 

TMPyP4 ....................................................................................8 

Index 

Tobramycin, Free Base ...................................................... 6 

TOFA ..........................................................................................85 

Tomatidine, HCl .................................................................. 63 

Topotecan, Hydrochloride ...................................................83 

N a -Tosyl-Phe Chloromethyl Ketone .................................95 

TPCK ...................................................................................... 3 

Trequinsin, Hydrochloride ................................................ 58 

Trichostatin A, Streptomyces sp. .......................................74 

InSolution Trichostatin A, Streptomyces sp................76 

TRIM ........................................................................................ 

Tripeptidylpeptidase II Inhibitor ..................................... 3 

TrkA Inhibitor ..........................................................................53 

Trypsin Inhibitor, Corn....................................................... 3 

Trypsin Inhibitor, Soybean ............................................... 3 

Trypsin Inhibitor, Soybean, High Activity .................... 3 

Tunicamycin, Streptomyces lysosuperficus ................. 48 

TX- 23 .............................................................................35, 53 

TX- 9 8 .....................................................................................8 

Tyrene CR4 ..............................................................................53 

Tyropeptin A, Synthetic .................................................... 38 

Tyrosine Kinase Inhibitor Set II .........................................54 

Tyrosine-Specific Protein Kinase Inhibitor .....................53 

U 

U0 24 .......................................................................................27 

U0 25 .......................................................................................27 

U0 26 .......................................................................................27 

U 8666A ............................................................................... 63 

U-73 22 ...................................................................................94 

U-73343 ..................................................................................94 

Ubiquitin Aldehyde ............................................................ 38 

UCH-L Inhibitor ................................................................ 38 

UCH-L3 Inhibitor ................................................................ 38 

V 

Valinomycin, Streptomyces fulvissimus ....................... 52 

D-Val-Phe-Lys Chloromethyl Ketone, 

Dihydrochloride ............................................................ 3 

Valproic Acid, Sodium Salt .................................................74 

VEGF Receptor 2 Kinase Inhibitor I ..................................53 

VEGF Receptor 2 Kinase Inhibitor II .................................53 

VEGF Receptor 2 Kinase Inhibitor III ...............................53 

InSolution VEGF Receptor 2 Kinase Inhibitor III......53, 84 

VEGF Receptor 2 Kinase Inhibitor IV ...............................54 

VEGF Receptor 2 Kinase Inhibitor V, ZM32388 ..........54 

VEGF Receptor 3 Kinase Inhibitor, MAZ5 .....................54 

VEGF Receptor Tyrosine Kinase Inhibitor .......................53 

VEGF Receptor Tyrosine Kinase Inhibitor II.............53, 54 

Vinpocetine .......................................................................... 58 

Vitamin E Succinate .............................................................4 

W 

W-5, Hydrochloride ....................................................30, 58 

W-7, Hydrochloride ....................................................30, 58 

W- 2, Hydrochloride ..................................................30, 58 

W- 3, Hydrochloride ..................................................30, 58 

WHI-P 80, Hydrochloride................................................... 7 

Wortmannin ............................................................................32 

X 

XG076 .................................................................................... 22 

XIAP, Human, Recombinant, E. coli ..................................65 

Y 

Y-27632 ...................................................................................57 

InSolution Y-27632 ...........................................................57 

Z 

Zaprinast ............................................................................... 58 

Zebularine ...............................................................................7 

Zinc (II) Protoporphyrin IX ................................................ 07 

(Z-LL) 2 Ketone...................................................................... 29 

ZM 336372 ......................................................................27, 55 


Phone 800 628 8470 


7

Index 

Numerical Index 

60 ......................................... 4 

38 ........................................ 25 

7 2 ...........................................95 

480 ..........................................94 

4995 ....................................... 43 

529 ...........................................39 

5677...........................................94 

57 ......................................... 6 

30967 .............................. 98, 28 

34 03 ..................................... 29 

34 5 ...................................... 42 

35675 ........................................60 

52332 ..................................... 30 

58346 ...................................... 6 

65035 ...................................... 3 

00050 ................................... 0 

0005 .................................... 0 

00068 .................................. 49 

00069 .................................. 49 

00 09 ......................................93 

00 22 ...................9, 29, 33, 43 

00 28 ......................................46 

0 500 ................................... 25 

0 50 ................................... 25 

04550 .....................................93 

08975 ................................... 30 

0 0 .................................... 44 

0 5 .................................... 44 

0 23 ...............................82, 9 

0 75.................................... 25 

4666 ......................................72 

4802 .................................... 37 

4803 .................................... 37 

6805 ......................................35 

68 3 ......................................33 

68 4 ......................................33 

68 6 ......................................33 

68 9 ......................................33 

6825 ......................................34 

6845 ................................... 39 

6850 ................................... 39 

84 5 .......................................79 

2 760 ......................................46 

2 76 ......................................47 

2 762 ......................................47 

2 765 ......................................47 

2 767 ......................................47 

2 790 ......................................48 

2 850 ......................................48 

24005 ........................................ 4 

24008 ........................................ 4 

24009........................................ 4 

240 ........................................ 4 

240 2 ........................................ 4 

240 3 ........................................ 4 

240 4 ........................................ 4 

240 5 ........................................ 4 

240 7 ........................................ 4 

240 8 ........................................ 4 

240 9 ........................................ 4 

24020 ........................................ 5 

26850 ................................... 30 

26870 ............................... 5, 9 

2687 ............................... 5, 9 

28 25 ............................... 5, 9 

28 35 ............................... 5, 9 

2974 ......................................72 

29875 ................................... 25 

29876 .......................... 4 , 59 

29935 ......................................72 

54500 ................................... 0 

55 00 ......................................48 

55200 .................................... 0 

64300 .....................................79 

64585 .....................................79 

64602 ................................... 26 

64640 ..................................... 5 

65350......................................79 

69756 .................................... 26 

7 260 ........................................ 5 

7 26 .................................5, 84 

7 58 ......................................96 

7 586 ......................................96 

7 587 ......................................96 

7 588 ......................................96 

7 589 ......................................96 

72050 ......................................73 

75580 ......................................48 

76880 ................................... 60 

76900 ......................................25 

7690 .................................... 3 

769 0 .................................... 3 

78 96 .................................... 26 

78220 .................................... 26 

7822 .................................... 26 

78223 .................................... 26 

7825 .......................... 8, 26 

78273 ......................................72 

78276 ......................................73 

7828 .................................... 26 

78488 ......................................67 

78494 ......................................67 

8 350 ...............................88, 9 

820 5 ......................................70 

82300......................................93 

82540 ................................... 4 

89250 .................................... 26 

89300.................................... 5 

89400 ..............................77, 82 

89422 .................................... 47 

89480 ....................................... 7 

89482 ....................................... 7 

89484 ....................................... 7 

89485 ....................................... 7 

89825 ......................................7 

90080 .................................. 62 

9 500 ...................................... 9 

94348 .....................................80 

94950 .....................................80 

96000 ......................... 0 , 42 

96322 ......................................9 

96805 .....................................67 

968 0 ......................................67 

968 ......................................67 

96870 ............................ 70, 54 

9687 ................................... 54 

96872 ............................ 70, 54 

9722 ......................................48 

97900 ................................... 04 

9900 .................................... 26 

200 00.................................... 47 

200484 ................................... 26 

200485 ................................... 26 

203290 .....................................37 

20329 ......................................37 

203292 .....................................37 

203293 .....................................37 

203294 .....................................37 

203297......................................37 

203303 .....................................37 

203305 .....................................42 

203350 .................................. 60 

203389 .................................. 42 

203390 .................................. 42 

20339 ................................... 42 

203392 .................................. 42 

203600 ..................................... 5 

20367 .................................... 5 

203694 .....................................59 

203695 .....................................59 

203696 .....................................48 

203697 .....................................48 

20370 ......................................59 

203704 .....................................48 

203705......................................59 

203850 ................................... 0 

203895 .................................. 42 

203900 .................................. 42 

2039 2 .................................... 

203984 .................................. 42 

203987 .....................................48 

203994 ................................... 47 

203996 ................................... 47 

205530 ................................... 27 

20553 .................................... 27 

205546 .................. 9 , 05, 8 

207000 .....................................59 

20700 ......................................59 

208665 ......................... 42, 57 

2087 0 ........................................ 7 

2087 ........................................ 7 

2087 9 ................. 5, 25, 37 

20872 .......................... 5, 25 

208722.................................... 5 

208724 .................................... 5 

208725......................................37 

208726.................................... 5 

20873 .................................... 6 

208733 ................................... 6 

208734 ....................................... 7 

208742 .................................... 5 

208743 .................................... 5 

208744 .................................... 5 

208745 .................................... 5 

208748 .................................... 6 

208750 ......................... 5, 25 

20877 .................................... 6 

208772.................................... 6 

20885 ......................................59 

208900 ......................... 5, 27 

20890 ................................... 5 

208902 ................................... 5 

208904 ................................... 5 

208920 ....................................... 7 

20892 ........................................ 7 

208925 .....................................82 

2 0 50 ......................................59 

2 0 55 ......................................59 

2 200 ................................... 54 

2 274 .................................... 54 

2 875 .................................... 4 

2 59 .................................... 5 

2 592 ................... 95, 0, 57 

2 6200 .................................... 5 

2 7359 .................................... 27 

2 7504 ......................................37 

2 769 ......................................59 

2 7692 ......................................59 

2 7695 ...................................... 5 

2 7696 ...................................... 5 

2 7697 ...................................... 5 

2 77 3 ...................................... 5 

2 77 4 ............................... 6, 9 

2 7720 ............................... 6, 20 

2 8696 ........................................ 9 

2 8697 ........................................ 9 

2 8699 ........................................ 9 

2 8705 .................................9, 84 

2 8706 .................................9, 84 

2 8708 ........................................ 9 

2 8723 ......................................64 

2 8728 ......................................65 

2 8729 ......................................64 

2 8735 ......................................64 

2 8742 ......................................64 

2 8744 ......................................64 

2 8745 ......................................64 

2 8746 ......................................64 

2 8747 ......................................64 

2 8750 ......................................64 

2 8753 ......................................65 

2 8755 ......................................65 

2 8757 ......................................65 

2 8759 .............................. 65, 66 

2 876 ......................................65 

2 8766 ......................................65 

2 8767 ......................................65 

2 8772 ......................................66 

2 8773 .............................. 65, 66 

2 8775 .................................... 47 

2 8776 ......................................65 

2 8784 ......................................64 

2 8806 ......................................66 

2 88 4 ......................................64 

2 8825 ......................................66 

2 8826 ......................................65 

2 8830 ......................................64 

2 8832 ......................................65 

2 8840 .............................. 65, 66 

2 884 ......................................65 

2 9002 ......................................64 

2 9005 ......................................65 

2 9007 ......................................64 

2 9009......................................65 

2 90 ......................................64 

2 90 2 ......................................65 

2 9372 .................................... 27 

2 9377 .................................... 27 

2 9379 .................................... 27 

2 938 .................................... 27 

2 9385 .................................... 27 

2 9393 ................................... 28 

2 94 5 .................................... 27 

2 94 7 .................................... 27 

2 94 9 .................................... 27 

2 9420 ................................... 28 

2 942 .................................... 27 

2 9426 .................................... 27 

2 9427 .................................... 27 

2 9428 ...................................... 7 

2 9433 ................................... 28 

2 9435 ................................... 28 

2 9442 ...................................... 6 

2 9445 ...................................... 6 

2 9448...................................... 6 

2 9457 ...................................... 5 

2 9469 ......................................70 

2 9470 ......................................70 

2 9476 ...................................... 6 

2 9477 ...................................... 6 

2 9479 ...................................... 5 

2 9495 ................................... 28 

2 9557 .............................. 88, 89 

220005 ................................... 5 

220285 .....................................38 

220485 ..................................... 2 

220486 ..................................... 2 

22055 ................................... 60 

220557 .................................. 20 

230790 .................................. 28 

230906 .................................. 28 

23 085 ................................... 57 

233 00 ......................................48 

233 05 ................................... 20 

233 65 ......................................96 

234 0 ......................................85 

234 40 .................................... 7 

234 47 .................................... 7 

234 64 .................................... 7 

234450 ................................8, 50 

234490 .....................................5 

23449 .....................................5 

234503 ..................................... 6 

234505 .....................................48 

234599 ................................... 47 

235420......................................64 

23542 ......................................64 

235422......................................64 

235423......................................64 

235427 ......................................64 

235429......................................66 

236005 .....................................86 

2360 ......................................86 

2360 2 ......................................86 

238590 .....................................49 

23880 ...................................... 6 

238802 ..................................... 6 

238803 ..................................... 6 

238804 ..................................... 6 

238900 .....................................34 

239763 ................................... 60 

239764 ................................... 60 

239765 ................................... 60 

239783......................................88 

239802 ...................... 49, 86, 9 

239803 .................................. 62 

239804 .................................. 62 

239805 .................................. 42 

239835 .....................................59 

239900 .....................................59 

24089 ................................... 28 

25 400 ......................................93 

25 40 ......................................93 

25 600 .................................9, 49 

25 650 ......................................49 

25 700 ................................... 28 

25 755 ......................................59 

25 756 ......................................59 

25 800 ......................................82 

2520 0 ...................................... 2 

252740 ...............................5, 5 

253300 .....................................59 

253500 .................................. 57 

257920 ......................................80 

25954 .................................... 47 

259544 ................................... 47 

259580 ................................... 47 

260575 ................................... 48 

260585 ...........................49, 44 

260684 .................................. 48 

260905 .....................................77 

260920 .....................................7 

260960 ..................................... 8 

26096 ..................................... 8 

260962 ..................................... 8 

260963 ..................................... 8 

260964 ..................................... 8 

2620 5 ......................................77 

263200 .....................................59 

263202 .....................................59 

263203 .....................................59 

263225......................................38 

264 55 ......................................64 

264 56 ......................................64 

265005 ................................... 0 

268295 ..............................34, 49 

286888 .................................. 42 

2878 5 ............................ 95, 28 

287840 ............................. 86, 96 

287845......................................86 

28789 ........................................ 9 

287895 ......................................43 

287897 ......................................22 

288 04 ................................... 39 

288500 .................................. 04 

2987 ......................................77 

300230 ..............................4 , 94 

300260 ................................... 0 

300265 .................................. 42 

300270 .....................................79 

3 0500 ...............................4 , 57 

3 203 .................................... 0 

3 204 .................................... 0 

3 250 ......................................60 

3 7200 ......................................49 

3 7500 ......................................86 

3 762 ................................... 28 

3 7638 ................................... 28 

322328 ................................... 57 

324380 ......................................83 

324473 ......................................79 

324483 .....................................86 

324503................................... 29 

32462 ................................... 42 

324622................................... 42 

324625 ................................... 29 

324626 ................................... 29 

324630 .................................. 57 

324673 ......................................49 

324680 .....................................80 

324683 ..................9, 34, 38, 83 

324688 .....................................83 

32469 ................................... 29 

324692.......................... 8, 29 

324693................................... 60 

324694 .....................................49 

324744 .......................... 8, 29 

324745 .......................... 8, 29 

324759 .................................... 8 

324760 ......................................60 

324800 ................................... 37 

32480 .................................... 37 

72 Orders Phone 800 854 34 7 


Fax 800 776 0999 


324875 ......................................92 

324880 ..............................7 , 80 

324890 .................................. 28 

32489 ................................... 28 

324895......................................60 

324905......................................83 

324930 ......................................49 

328000 .....................................25 

328005 .....................................25 

328006 .....................................25 

3298 5 ................................... 60 

330005 ......................... 6, 29 

330200 .................................. 29 

33 500 ................................... 57 

34 80 .................................... 0 

34 205 ......................................83 

34 206 ......................................83 

34 207 ...............................3 , 93 

34 2 .................................... 54 

34 246 .................................... 5 

34 248 ......................................88 

34 249 ......................................88 

34 25 ...................................... 6 

34 29 ......................................67 

34 325 ......................................88 

34 380 ......................................60 

342000 ........................... 64, 27 

344036 .....................................48 

344079 ............................. 86, 96 

344085 .................................. 42 

344095 .....................................89 

344 50 ................................... 44 

344 52 ................................... 45 

344 54 ................................... 45 

344280 .....................................60 

3445 0 ................................... 45 

3445 2 ................................... 45 

3445 4 ................................... 45 

344550 .................................. 45 

344555 .................................. 45 

344557 .................................. 45 

344559 .................................. 45 

344850 .....................................95 

344930 ................................... 8 

34493 ................................... 8 

344960 .................................. 29 

345670 .....................................98 

345805 ........................... 49, 49 

3458 0 ................................... 60 

3458 2 .................................... 6 

3458 4 ......................................95 

345834 ...................... 49, 83, 96 

345836 .....................................49 

345878 .................................. 45 

345880 .................................. 46 

345882 .................................. 46 

345883 .................................. 46 

345884 .................................. 46 

345885 .................................. 46 

347436 ................................... 29 

349254 .....................................87 

36 540 ......................................20 

36 54 ......................................20 

36 542 ......................................20 

36 545 ......................................2 

36 546 ......................................2 

36 547 ......................................20 

36 548 ......................................20 

36 549 ......................................20 

36 550 ...................................... 6 

36 550 ......................................20 

36 55 ......................................20 

36 552 ............................... 6, 20 

36 553 ......................................20 

36 554 ......................................20 

36 555 ......................................20 

36 556 ......................................20 

36 557 ...............................20, 84 

364200 .................................. 20 

364205 .................................. 20 

364206 .................................. 20 

3642 0 ................................... 20 

365250 .....................................38 


36525 ......................................38 

365252...............................29, 38 

365253 .....................................38 

368050 ............................. 65, 66 

368055 ............................. 65, 66 

368056 ............................. 65, 66 

368620 .....................................65 

369334 .................................. 29 

370654 .....................................44 

370655 .....................................44 

370666 .....................................43 

370674 ......................................43 

370677 ......................................43 

370679 ......................................43 

37 7 5 .......................... 46, 54 

37 806 ......................................49 

37 955 ....................... 34, 38, 44 

37 956 ......................................38 

37 957 ............................... 2, 2 

37 958 ......................................34 

37 96 .............................. 34, 44 

37 962 .................................9, 34 

37 963 .............................7, 9, 34 

37 964 .......................... 7, 34, 44 

37 966 ......................................44 

37 970 ....................... 34, 44, 56 

37 980 .................................... 0 

372770 ......................................38 

373225 .................................... 37 

373250 ................................... 29 

373260 ................................... 49 

373265 ................................... 49 

374000 .................................. 54 

375670 ......................................49 

3768 6 .................................... 5 

377230 ......................................92 

377980......................................38 

382 35 ................................... 29 

382 47 ......................................73 

382 48 ......................................74 

382 49 ......................................74 

382 65 ......................................75 

382 66 ......................................75 

382 67 ......................................75 

382 68 ......................................75 

382 69 ......................................75 

382425 ................................... 58 

385880 ........................... 25, 49 

385883 .....................................72 

385885 .....................................98 

385886 .....................................98 

390238 .....................................82 

39060 .................................. 46 

390602 .....................................56 

393204 .................................. 42 

397 00 ......................................49 

399250 .................................. 04 

399275 ................................... 04 

4000 0 .....................................64 

4000 ......................................64 

4000 2 .....................................64 

4000 5 .....................................64 

4000 9 .....................................64 

400022 .....................................64 

40005 ................................... 6 

400076 .............................. 0, 38 

400079 .................................. 43 

400085 ....................... 6, 2 , 26 

400090 ..................................... 0 

400 40 .....................................67 

400600 ................................... 0 

40 003 .....................................87 

40 006 .................................. 54 

40 474 ................................... 54 

40 477 ................................... 54 

40 478 ................................... 54 

40 479 ................................... 55 

40 480................................... 55 

40 48 ................................... 55 

40 482................................... 55 

40 483................................... 55 

40 485................................... 55 

40208 ..................................... 7 

402085 .............................. 7, 2 

402086 .............................. 7, 2 

402088 .............................. 7, 2 

405268 .....................................87 

405269 .....................................87 

405270 .....................................87 

40527 ......................................87 

406 70 ......................................23 

407247 ......................................49 

4077 0 ................................... 29 

407850 .....................................79 

407900 .....................................26 

4 0957 ................................... 58 

4 6 57 ................................... 55 

4 6200 ................................... 28 

4 9650 ......................................93 

4 9800 ......................................79 

4 9840 ......................................74 

420097 ............................. 50, 84 

420099 .....................................50 

420 0 ......................................50 

420 04 ......................................50 

420 06 ......................................50 

420 2 ......................................50 

420 6 ......................................22 

420 8 ......................................22 

420 9 ......................................22 

420 2 ......................................50 

420 22 ......................................50 

420 23 ......................................22 

420 26 ......................................50 

420 28 ......................................22 

420 29 ......................................23 

420 30 ......................................22 

420 3 ......................................23 

420 32 ......................................50 

4202 0 ................................... 62 

420297 ............. 7, 29, 34, 38, 44 

420298............. 7, 29, 34, 38, 44 

420305 .....................................38 

4203 .................................... 6 

4203 9 ................29, 34, 38, 44 

420320......................................34 

42032 ......................................44 

420323......................................34 

420345 .....................................87 

4204 .................................... 6 

420600 .....................................92 

42 050 ................................... 29 

422000 .............................. 7, 2 

422500 .................................. 48 

422685................................... 30 

422686................................... 30 

422688................................... 30 

422706 ........................................ 7 

422708 ........................................ 7 

422709 ........................................ 7 

4227 ........................................ 7 

4227 2 ........................................ 7 

422720 ................................... 46 

426 00 .................................... 37 

426 02 .................................... 37 

426 04 .................................... 37 

428 50 ......................................50 

428 60 ......................................50 

428205 ......................................50 

43 050 ......................................76 

43 05 ......................................76 

432077................................... 30 

43474 ...............................86, 92 

435300 .....................................50 

43530 .....................................50 

435302 .....................................50 

43770 ......................................90 

438 85 ......................................89 

438 86 ......................................89 

440025 .................................. 05 

440202 .....................................3 

440203 .....................................3 

440204 .....................................3 

440205 .................................. 06 

44 25 ................................... 30 

444042 .................................. 48 

444 68 ................................... 40 

444 69 ................................... 40 

444 70 ............................95, 46 

444 80 ......................................28 

444 85 ......................................28 

444 90 ......................................28 

444200 .................................. 40 

4442 8 .................................... 2 

444225 ................................... 2 

444237 ................................... 2 

444238 ................................... 2 

444239 ................................... 2 

444240 ................................... 2 

44424 .................................... 2 

444242.................................... 2 

444243 ................................... 2 

444244 .................................. 20 

444247 ................................... 20 

444249 ................................... 2 

444250 .................................. 20 

44425 .................................... 2 

444252 .................................. 22 

444253 .................................. 22 

444260 ................................... 2 

444264 .................................. 20 

444265 ................................... 2 

44427 ................................... 20 

444274 .................................... 2 

444278 .................................. 22 

444280 ................................... 2 

44428 ................................... 2 

444283 .................................. 22 

444285 ................................... 2 

444286 .................................. 20 

444300 ................................... 0 

444600 ................................... 0 

444605 ...........................38, 40 

444800 .....................................87 

444898 .................................. 43 

444937 .....................................26 

444938 .....................................26 

444939 .....................................26 

445800 .....................................83 

445825 .................................. 30 

448 0 ......................................50 

4537 0 ......................................28 

454202 .................................. 58 

454559 .....................................72 

454565 .....................................93 

457250 .................................. 06 

4596 6 ......................................60 

4596 8 ......................................6 

459620 .....................................6 

466220 ................................... 0 

472804.................................... 0 

474700 ......................................89 

474705 ......................................89 

474780 .................................... 37 

474790 .......................... 0 , 37 

47479 .................................... 37 

474925 ................................... 58 

475250 ................................... 58 

475740 ......................................90 

475800......................................26 

4758 4 ......................................60 

4758 5 ......................................60 

4758 6 ......................................60 

4758 8 ......................................60 

47582 ......................................60 

475837 ................................... 63 

475840 .................................. 58 

475863 ......................................26 

475865 ......................................94 

475876 ................................... 52 

475880 ......................................29 

475882 ......................................29 

475883 .................................... 0 

475886 .................................... 

475889 ......................................92 

475892 .................................... 0 

475950 ......................................60 

475975 ................................... 43 

47598 ......................................29 

Index 

476475 ......................................39 

476480 .....................................39 

476485......................................35 

476493......................................23 

476880 ........................................ 5 

479775 ......................................60 

4799 5 ................................... 43 

479975 ......................................92 

480025 .................................. 55 

480030 .................................. 55 

480060 .....................................68 

480065 .....................................68 

480066 .....................................68 

480 00 .....................................94 

480403 .....................................60 

48 406................................... 55 

48 407 ................................... 55 

48 408................................... 56 

48 480 ................................... 56 

48 486 ................................... 56 

48 500......................................39 

48 987 ...............................87, 97 

482 00 .................................... 

482240 ................................... 37 

48225 ......................................60 

482650 ................................... 2 

482655 ................................... 2 

482700 ................................... 2 

482702 ................................... 2 

482760 ................................... 2 

483 20 .................................... 

483 25 .................................... 

483400 ................................... 

484 00 ....................... 23, 26, 87 

484235 ................................... 

484500 ................................... 

490070 ................................... 

490075 ................................... 2 

49 207 ......................................72 

492025 ................................... 37 

492030 .................................. 06 

493800 .....................................79 

495320 .................................. 06 

495455 ......................... 43, 5 

495604 .....................................60 

495609 .....................................60 

495620 ..................................... 7 

49562 ...................................... 7 

495622 ..................................... 7 

495623 ..................................... 7 

495624...................................... 7 

496000 .................................. 0 

496 00................................... 43 

496 50 ......................................67 

4969 5 ................................... 56 

499600 .....................................5 

499700 .....................................74 

506 2 ......................................26 

506 26 ......................................26 

506 32 ......................................67 

506 34 ......................................67 

506 48...............................26, 84 

506274 ......................................94 

5 2729 ......................................79 

5 2732 ................................... 56 

5 2774 .................................... 

5 3000 ......................................26 

5 302 .................................... 6 

5 3022 .................................... 6 

5 3024 .................................... 6 

5 3030 ......................................26 

5 3032 ......................................5 

5 3033 ......................................5 

5 3035 ......................................5 

5 3036 ......................................84 

5 3040 ......................................5 

5 3 00 ................................... 48 

5 6354 ......................................70 

5 648 ................................... 30 

5 6485 ................................... 0 

5202 9 ................................... 30 

520222 .................................. 30 

520224 ................................... 30 


Phone 800 628 8470 


73

Index 

52 000 ......................................6 

52 230 ......................................5 

52 23 ......................................5 

52 232 ......................................5 

5233 0 ......................................87 

52437 ......................................90 

524390................................... 43 

524403 .....................................89 

524488 .....................................39 

524620......................................6 

524624 ......................................62 

524625......................................62 

524627 ......................................62 

524628......................................62 

5247 4 ................................... 58 

5247 7 ................................... 58 

5247 8 ................................... 58 

525 43 ......................................94 

525 45 ......................................94 

525276 ................................... 30 

525325......................................62 

527948 ................29, 34, 39, 5 

528 06 ......................................3 

528 08 ......................................32 

528 20 ......................................80 

528 40 ...................................... 7 

528 50 ......................................79 

528205 .................................. 59 

528208 .................................. 59 

5282 3 ................................... 59 

5282 4 ................................... 59 

528820 .....................................79 

529570 ........................... , 56 

529573......................................5 

529574 ......................................5 

529576 ......................................5 

529579......................................5 

52958 ................................. 8, 5 

535 40 ................................... 35 

535 4 ................................... 35 

535 42 ................................... 35 

5370 0 ................................... 30 

5370 .................................... 3 

537200 ................................... 

539 24 ................................... 34 

539 28 ................................... 34 

539 29 ................................... 34 

539 3 ................................... 32 

539 32 ................................... 32 

539 33 ................................... 33 

539 34 ................................... 32 

539 36 ................................... 33 

539 37 ................................... 33 

539 38 ................................... 34 

539 60 .................................... 37 

539 6 ................................... 38 

539 62 ................................... 38 

539 63 ................................... 38 

539 64 ................................... 38 

539 65 ................................... 38 

539 75 ................................... 38 

539 79 ................................... 38 

539209 ......................... 46, 60 

5395 6 ......................................6 

539522 .....................................40 

539542 .....................................40 

539552 .....................................6 

539560 .....................................39 

539572......................................42 

539573 .....................................42 

539604 .....................................39 

5396 0 ......................................39 

539620 .....................................6 

539624......................................39 

539630 .....................................62 

539634 .....................................39 

539636 .....................................39 

539638 .....................................6 

53965 ......................................42 

539652 .....................................39 

539654 .....................................39 

539658 .....................................42 

539677 .....................................42 

539678 .....................................42 

539679 .....................................42 

539684 .....................................35 

539685 .....................................42 

539686 .....................................42 

539687 .....................................42 

539690 ......................... 60, 6 

53974 ......................................6 

540200 .....................................6 

540205 .....................................6 

5402 0......................................6 

5402 ......................................6 

5402 5 ......................................6 

540222 ................................... 6 

5404 .................................... 6 

540500 ..................................... 7 

548000 ................................... 

55 476 ......................................65 

55 600 ...............................32, 94 

55 850 ...............................94, 98 

553003 .....................................55 

553008 .....................................55 

5532 ......................................84 

553400 ..............................52, 87 

553590 .....................................77 

554325 ..............................87, 97 

554725 ......................................52 

555550 .....................................56 

55555 ......................................56 

555552 ............................. 56, 84 

555553 .....................................56 

555554 .....................................56 

55688 .....................................77 

556883 .....................................77 

557303 .....................................72 

557322......................................6 

557330 .................................. 58 

557360 ..................................... 7 

557362...................................... 7 

557364 ..................................... 7 

557368 ................................... 5 

557370 ......................................40 

557403......................................72 

557440 .................................. 52 

557502 .................................. 58 

557508 .....................................40 

557509 .....................................40 

5575 4 ......................................40 

557520 ...............................2 , 40 

55752 ......................................40 

557525 ......................................40 

557550 ........................... 92, 38 

55755 ................................... 38 

559300 .....................................40 

559303 .................................. 63 

559307 .....................................40 

559387 .....................................27 

559388 .....................................26 

559389 .....................................27 

559396 .....................................27 

559397 .....................................26 

559398 .....................................27 

559399 .....................................27 

559400 .....................................27 

559402 ..................................... 2 

559403 .....................................26 

559404 .....................................27 

559407 .....................................27 

5594 8 ......................................74 

56 308 ......................................70 

565000 .................................. 34 

5656 0 ......................................87 

565625 .....................................27 

5657 5 ............................... 2, 4 

565730 .....................................74 

565749 ................................... 0 

565750 .................................. 0 

565755................................... 0 

565760 .................................. 0 

56576 ................................... 0 

565762................................... 0 

565763 .................................. 0 

565765................................... 03 

565766................................... 03 

565768 .................................. 02 

565770................................... 02 

56577 ................................... 02 

565772................................... 02 

565773 .................................. 02 

565774 ................................... 02 

565775 ................................... 02 

565777 .................................. 02 

565778................................... 02 

565780 .................................. 0 

565784 .................................. 02 

565787................................... 03 

565788 .................................. 0 

565789 .................................. 03 

565790 .................................. 03 

565833 .................................. 52 

566320 .....................................74 

56632 ......................................74 

567020 .....................................89 

56702 ......................................89 

56705 ......................................7 

567300 ................................... 

567305 ....................... 27, 87, 92 

567540 .....................................6 

567565 .....................................62 

567570 .................................... 6 

567630 .....................................87 

5677 5 ......................................95 

567725......................................40 

567726......................................40 

56773 ......................................57 

567750 .....................................74 

567790 ..............................52, 94 

567805 .....................................52 

567806 .....................................52 

5678 6 ......................................54 

568500 .................................. 40 

569396 .....................................35 

569397 ................29, 35, 4 , 44 

569620 .................................. 63 

570250....................................5, 8 

572625 ......................................52 

572630......................................52 

572632......................................52 

572635......................................52 

572636......................................52 

572650 ..................................... 7 

572660 .....................................52 

572888......................................52 

573500 ......................... 05, 56 

574 00 ......................................88 

574 02 ......................................88 

574 05 ......................................88 

574625 .....................62, 83, 43 

5747 .......................................52 

5747 2 ......................................52 

574775 ................................... 48 

579000 .....................................4 

579002 .....................................4 

579050 ................................... 7 

57905 .................................... 7 

579052 ................................... 4 

579053 ................................... 7 

580550 .....................................62 

58055 ......................................62 

58 004......................................8 

58 006......................................8 

58 007 ......................................8 

58 0 ......................................8 

58 800 ......................................4 

58 8 0 ......................................53 

5834 .................................... 6 

586005 .................................. 43 

589400 .....................................53 

5894 .................................... 

598226 ................................... 6 

5985 0 .......................... 22, 4 

6 2080 ................................... 23 

6 2084 ................................... 23 

6 2 00 ......................................79 

6 3450 ......................................85 

6 3560 ......................................8 

6 3570 ................................... 56 

6 357 ................................... 56 

6 4005.................................... 6 

6 4350 ................................... 63 

6 4800......................................83 

6 6370 .................................... 26 

6 637 .................................... 26 

6 6382 .................................... 3 

6 6387 ............................ 95, 3 

6 6399 .................................... 26 

6 645 ...............................53, 57 

6 6452 ...............................53, 57 

627608 .....................................64 

627609 .....................................64 

6276 0 ......................................64 

627624 .................................... 3 

643500 ................................... 

645905 ................................... 3 

647925 ......................................74 

647926 ......................................74 

648450 .....................................53 

650345 ................................... 3 

650357 ................................... 3 

654380 .................................. 48 

655200 ............................. 35, 53 

655203 ....................................... 8 

655230 .....................................53 

657008 .................................. 38 

6570 5 ......................................53 

65702 ......................................54 

658390 .....................................46 

658395 .....................................46 

658400 .....................................46 

65840 .....................................46 

658402 .....................................47 

658403 .....................................47 

658404 .....................................47 

658405 .....................................46 

658406 .....................................47 

658407 .....................................47 

658408 .....................................46 

658409 .....................................47 

6584 0 ......................................46 

6584 5 ......................................47 

6584 7 ......................................47 

6584 8 ......................................47 

658425 .....................................46 

658430 .....................................46 

658440 .....................................46 

658450 .....................................46 

658452 .....................................25 

658460 .....................................47 

658520 ............................. 48, 82 

658548 .....................................48 

658550 .....................................47 

65855 ......................................48 

658552 .....................................48 

658553 .....................................48 

662005 .....................................27 

662006 .....................................27 

662008 .....................................27 

6620 5 ................................... 63 

662035 .....................................94 

66204 ......................................94 

662056 .................................. 38 

662086 .................................. 38 

662089 .................................. 38 

676377 ................................... 52 

676380 .....................................74 

676475 ......................................53 

676480 .....................................53 

67648 .............................. 53, 54 

676485 .....................................53 

676487 .....................................53 

676489 .....................................54 

676492 .....................................54 

676497......................................54 

676498 ............................. 53, 84 

677500 .................................. 58 

679 30 ......................................4 

68 500 ...................................... 7 

68 625 ............................ 30, 58 

68 629 ......................................30 

68 629 ................................... 58 

68 635 ............................ 30, 58 

68 636 ............................ 30, 58 

68 675 ......................................32 

682300 .................................. 22 

684500 .................................. 58 

688000 .....................................57 

68800 .....................................57 

69 400......................................7 

69 550 ................................... 07 

692000 ..............................27, 55 

09587 ...................................39 

03-34-0002 ............................70 

03-34-0027 ............................70 

03-34-0029 ............................70 

03-34-0035 ............................70 

03-34-005 ................ 5, 27 

03-34-0052 ............................70 

03-34-0055 ............................70 

05-23-0 0 .......................... 39 

05-23-030 .......................... 4 

05-23- 70 .............................70 

05-23-4904 ............................39 

CBA003.................................. 22 

CBA042 .................................. 03 

PF0 9 ...................................... 23 

PF020 ..................................... 23 

PF02 ..................................... 23 

PF095 ..................................... 23 

PF096 ...................................... 24 

PF097 ...................................... 24 

PF098 ..................................... 23 

PF 22 ................................. 65, 66 

PF 37 .........................................65 

QIA40 ...................................... 24 

QIA54 ...................................... 24 

QIA55 ..................................... 22 

QIA56 ..................................... 22 

QIA63 ..................................... 22 

QIA73 ..................................... 22 

QIA 9 .................................... 49 

QIA 20 .................................... 6 

QIA 30 ................................... 22 

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Trademarks 

CALBIOCHEM®

Trademarks/Patent & Licensing Information 

Patent & Licensing Information, continued 

Patent & Licensing 

Statement Product Name Cat. No. 

Sold under license of 

Patent DE 3,802,865.4 

issued to BIOLOG LSI. 

Sold for research 

purposes only, pursuant 

to an agreement with 

GlaxoSmithKline. 

Sold under license from 

Michigan State University. 


Monophosphorothioate, 8-Bromo-2´monobutyryl-, 



Monophosphorothioate, 8-Bromo-, 



Monophosphorothioate, 8-Chloro-, 



Monophosphorothioate, 2´-O- 

Monobutyryl-, Rp-Isomer, Sodium Salt 


Monophosphorothioate, Rp-Isomer, 



Monophosphorothioate, 8-Bromo-, 


68 3 

68 6 

68 9 

6825 

370666 

370674 

N-SMase Inhibitor, GW4869 5677 5 

Chk2 Inhibitor 220485 

Patent & Licensing 

Statement Product Name Cat. No. 

Sold under license from 

Novartis Pharma AG. 

Sold under license of PCT 

Application W098/22, 03. 

Manufactured by Daiichi 

Fine Chemical Co., Ltd. 

Manufactured exclusively 

by Peptides International, 

Louisville, Kentucky, USA. 

Cdk Inhibitor, CGP745 4A 2 7696 

JAK3 Inhibitor IV 

JAK3 Inhibitor V 

ZM 336372 

TIMP- , Recombinant, Human 

TIMP- , Recombinant, Bovine 

TIMP- ELISA Kit 

MMP- ELISA Kit 

TAPI-0 

TAPI- 

TAPI-2 

420 2 

420 22 

692000 

PF0 9 

PF020 

QIA54 

QIA55 

579050 

57905 

579052 

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The list includes inhibitors of: 

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• Kinases: 

Akt, GSK-3, IKK, MAPK/MEK, PI 3-K, 

PKCs, PTKs, ROCK, etc. 

• Lipid Signaling 

• Nitric Oxide Synthases 

• Proteases: 

Calpains, Cathepsins, MMPs, Secretases, etc. 

• Protein Phosphatases 

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