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Soluble guanylate cyclase (sGC) is the primary cellular receptor for nitric oxide (NO). NO binds and activates a heme group in sGC, initiating the conversion of GTP to the second messenger cyclic GMP (cGMP). BAY 41-8543 is a heme-dependent stimulator of sGC, increasing the activity of recombinant sGC dose-dependently, from 0.1 nM to 100 µM, up to 92-fold. Surprisingly, NO donors synergize with BAY 41-8543 in stimulating recombinant sGC. BAY 41-8543 relaxes vessels and inhibits platelet aggregation in vitro at nM concentrations. In vivo, BAY 41-8543 decreases blood pressure dose-dependently, prolongs bleeding time, and reduces thrombosis. Inhalation of microparticles containing BAY 41-8543 increases pulmonary vasodilation without changing mean arterial pressure, suggesting that agonists of sGC may be efficacious in treating pulmonary hypertension.Formal Name: 2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-(4-morpholinyl)-4,6-pyrimidinediamine. CAS Number: 256498-66-5. Molecular Formula: C21H21FN8O. Formula Weight: 420.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 3 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml. lambdamax: 212, 327 nm. SMILES: FC(C=CC=C1)=C1CN2N=C(C3=NC(N)=C(N4CCOCC4)C(N)=N3)C5=C2N=CC=C5. InChi Code: InChI=1S/C21H21FN8O/c22-15-6-2-1-4-13(15)12-30-21-14(5-3-7-25-21)16(28-30)20-26-18(23)17(19(24)27-20)29-8-10-31-11-9-29/h1-7H,8-12H2,(H4,23,24,26,27). InChi Key: AQYFUZRYBJBAGZ-UHFFFAOYSA-N.
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