Inhibitor SourceBook™ Second Edition

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Cell Division/Cell Cycle/Cell Adhesion 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 Product Cat. No. Comments Size Price 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 Calbiochem • Inhibitor SourceBook Fax 800 776 0999 Web www.emdbiosciences.com/calbiochem
Nuclear Import/Export Inhibitors, continued Calbiochem • Inhibitor SourceBook Cell Division/Cell Cycle/Cell Adhesion Product Cat. No. Comments Size Price 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 Product Cat. No. Comments Size Price 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 Inhibitor 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 Technical Support Phone 800 628 8470 E-mail calbiochem@emdbiosciences.com 77
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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
Page 27 and 28: Mitogen-Activated Protein (MAP) Kin
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Page 31 and 32: Myosin Light Chain Kinase (MLCK) In
Page 33 and 34: Phosphatidylinositol 3-Kinase (PI 3
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Page 37 and 38: Protein Kinase A (PKA; cAMP-Depende
Page 39 and 40: Isozyme Specificities of Selected P
Page 41 and 42: Protein Kinase C (PKC) Inhibitors,
Page 47 and 48: Protein Tyrosine Kinase (PTK) Inhib
Page 57 and 58: Raf Kinase Inhibitors Raf kinases a
Page 59 and 60: Rho Kinase (ROCK) Inhibitors, conti
Page 61 and 62: Protein Phosphatase Inhibitors Calb
Page 63 and 64: Protein Phosphatase Inhibitors, con
Page 65 and 66: Apoptosis Caspase Inhibitors Activa
Page 67 and 68: Caspase Inhibitors, continued Produ
Page 69 and 70: Other Selected Inhibitors of Apopto
Page 73 and 74: DNA Methyltransferase Inhibitors DN
Page 75 and 76: Histone Acetylase and Deacetylase I
Page 77: Related Products Histone Deacetylas
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 and 120: Collagenase Inhibitors (Also see Ma
Page 121 and 122: Matrix Metalloproteinase (MMP) Inhi
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
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Protease Inhibitors, continued Calb
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Protease Inhibitors, continued Calb
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Protease Inhibitors, continued Sele
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Protease Inhibitor Cocktails, conti
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N Animal-Free Protease Inhibitor Co
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Proteasome and Ubiquitination Pathw
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Transmembrane receptors of various
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Angiotensin-Converting Enzyme (ACE)
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ATPase Inhibitors, continued Calbio
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Inhibitors of Glycoprotein Processi
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Heat Shock Protein Inhibitors Heat
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Inhibitors of Mitochondrial Functio
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NF-kB Activation Inhibitors NF-kB,
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NF-kB Activation Inhibitors, contin
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Phosphodiesterase (PDE) Inhibitors
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Plasminogen Activator Inhibitors Ti
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Protein Synthesis Inhibitors, conti
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Sonic Hedgehog Signaling Inhibitors
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Why can’t I make serial dilutions
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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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