Inhibitor SourceBook™ Second Edition

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Cell Division/Cell Cycle/Cell Adhesion DNA and RNA Polymerase Inhibitors DNA polymerases build DNA by forming a phosphodiester bond between the 5´a-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 5´a-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. Product Cat. No. Comments Size Price Actinomycin D, Streptomyces sp. 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 Inhibitor 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 Calbiochem • Inhibitor SourceBook Fax 800 776 0999 Web www.emdbiosciences.com/calbiochem 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 Calbiochem • Inhibitor SourceBook Cell Division/Cell Cycle/Cell Adhesion 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. Product Cat. No. Comments Size Price 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 Inhibitor I 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 Technical Support Phone 800 628 8470 E-mail calbiochem@emdbiosciences.com 73
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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)
Page 23 and 24: Glycogen Synthase Kinase Inhibitors
Page 25 and 26: c-Jun N-Terminal Kinase (JNK/SAP Ki
Page 27 and 28: Mitogen-Activated Protein (MAP) Kin
Page 29 and 30: MAP Kinase Inhibitors, continued Ca
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: DNA Methyltransferase Inhibitors DN
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 and 120: Collagenase Inhibitors (Also see Ma
Page 121 and 122: Matrix Metalloproteinase (MMP) Inhi
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Tissue Inhibitors of Matrix Metallo
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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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