Inhibitor SourceBook™ Second Edition

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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. Product Cat. No. Comments Size Price 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. Caffeic Acid 205546 (3,4-Dihydroxycinnamic Acid) 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 Calbiochem • Inhibitor SourceBook Fax 800 776 0999 Web www.emdbiosciences.com/calbiochem mg 5 mg $74 $287 500 mg $48 mg $92 5 mg $98 5 mg $ 04 mg $68 Product Cat. No. Comments Size Price 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). Calbiochem • Inhibitor SourceBook 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 Technical Support Phone 800 628 8470 E-mail calbiochem@emdbiosciences.com 9
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Inhibitor SourceBook Second Editio
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Calbiochem • Inhibitor SourceBook
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Akt (Protein Kinase B) Inhibitors,
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Calmodulin-Dependent Protein Kinase
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Casein Kinase (CK) Inhibitors Casei
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Checkpoint Kinase Inhibitors Eukary
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Cyclin-Dependent Kinase (Cdk) Inhib
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Glycogen Synthase Kinase-3 (GSK-3)
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Glycogen Synthase Kinase Inhibitors
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c-Jun N-Terminal Kinase (JNK/SAP Ki
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Mitogen-Activated Protein (MAP) Kin
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MAP Kinase Inhibitors, continued Ca
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Myosin Light Chain Kinase (MLCK) In
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Phosphatidylinositol 3-Kinase (PI 3
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Protein Kinase A (PKA; cAMP-Depende
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Isozyme Specificities of Selected P
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Protein Kinase C (PKC) Inhibitors,
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Protein Tyrosine Kinase (PTK) Inhib
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Raf Kinase Inhibitors Raf kinases a
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Rho Kinase (ROCK) Inhibitors, conti
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Protein Phosphatase Inhibitors Calb
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Protein Phosphatase Inhibitors, con
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Apoptosis Caspase Inhibitors Activa
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Caspase Inhibitors, continued Produ
Page 69 and 70: Other Selected Inhibitors of Apopto
Page 71 and 72: Calbiochem • Inhibitor SourceBook
Page 73 and 74: DNA Methyltransferase Inhibitors DN
Page 75 and 76: Histone Acetylase and Deacetylase I
Page 77 and 78: Related Products Histone Deacetylas
Page 79 and 80: Nuclear Import/Export Inhibitors, c
Page 83 and 84: Telomerase Inhibitors, continued Ca
Page 85 and 86: Topoisomerase Related Inhibitors, c
Page 87 and 88: Lipid Signaling Acetyl-CoA Carboxyl
Page 89 and 90: Cyclooxygenase (COX) Inhibitors, co
Page 91 and 92: HMG-CoA (3-Hydroxy-3-Methylglutaryl
Page 93 and 94: Lipoxygenase (LOX) Inhibitors Lipox
Page 95 and 96: Phospholipase Inhibitors Several si
Page 97 and 98: Sphingomyelinase Inhibitors Ceramid
Page 99 and 100: Amyloidogenesis Inhibitors Calbioch
Page 101 and 102: Secretase Inhibitors Deposition of
Page 103 and 104: Secretase Inhibitors Calbiochem •
Page 107 and 108: Glutathione S-Transferase (GST) Inh
Page 109 and 110: Guanylate Cyclase Inhibitors, conti
Page 111 and 112: Characteristics of various forms of
Page 113 and 114: Nitric Oxide Synthase (NOS) Inhibit
Page 115 and 116: Proteases Anthrax Lethal Factor (LF
Page 117 and 118: the ratio of active (76 kDa) to ina
Page 119: Collagenase Inhibitors (Also see Ma
Page 123 and 124: Matrix Metalloproteinase Inhibitors
Page 125 and 126: Tissue Inhibitors of Matrix Metallo
Page 127 and 128: Protease Inhibitors The proper func
Page 129 and 130: Protease Inhibitors, continued Calb
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Page 133 and 134: Protease Inhibitors, continued Sele
Page 135 and 136: Protease Inhibitor Cocktails, conti
Page 137 and 138: N Animal-Free Protease Inhibitor Co
Page 139 and 140: Proteasome and Ubiquitination Pathw
Page 141 and 142: Transmembrane receptors of various
Page 143 and 144: Angiotensin-Converting Enzyme (ACE)
Page 145 and 146: ATPase Inhibitors, continued Calbio
Page 149 and 150: Inhibitors of Glycoprotein Processi
Page 151 and 152: Heat Shock Protein Inhibitors Heat
Page 153 and 154: Inhibitors of Mitochondrial Functio
Page 155 and 156: NF-kB Activation Inhibitors NF-kB,
Page 157 and 158: NF-kB Activation Inhibitors, contin
Page 159 and 160: Phosphodiesterase (PDE) Inhibitors
Page 161 and 162: Plasminogen Activator Inhibitors Ti
Page 163 and 164: Protein Synthesis Inhibitors, conti
Page 165 and 166: Sonic Hedgehog Signaling Inhibitors
Page 167 and 168: Why can’t I make serial dilutions
Page 169 and 170: Calpastatin, Human, Recombinant, Do
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InSolution Microcystin-LR, Microcys
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RNA Polymerase III Inhibitor ......
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324875 ............................
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Trademarks CALBIOCHEM®
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Your #1 Resource for Inhibitors! We
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