Inhibitor SourceBook™ Second Edition

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Nitric Oxide/Oxidative Stress 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 Product Cat. No. Comments Size Price 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 Calbiochem • Inhibitor SourceBook Fax 800 776 0999 Web www.emdbiosciences.com/calbiochem 5 mg 25 mg $69 $263 g $33 5 mg $ 50 0 mg $ 27
Guanylate Cyclase Inhibitors, continued Calbiochem • Inhibitor SourceBook Nitric Oxide/Oxidative Stress Product Cat. No. Comments Size Price 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 Technical Support Phone 800 628 8470 E-mail calbiochem@emdbiosciences.com 07
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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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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 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: Glutathione S-Transferase (GST) Inh
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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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
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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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