Vericiguat

• CAS: 1350653-20-1
• Catalog Number: ACM1350653201
• Category: Others
• Molecular Weight: 426.39
• Molecular Formula: C19H16F2N8O2
• Description: Vericiguat, also known as BAY1021189 or BAY10-21189, is a potent and orally active sGC stimulator (Soluble Guanylate Cyclase Stimulator). Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD).
• Synonyms: BAY1021189; BAY 1021189; BAY-1021189; BAY10-21189; BAY-10-21189; BAY 10-21189; Vericiguat
• IUPAC Name: methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate
• Canonical SMILES: O=C(OC)NC1=C(N)N=C(C2=NN(CC3=CC=CC=C3F)C4=NC=C(F)C=C42)N=C1N
• InChI: InChI=1S/C19H16F2N8O2/c1-31-19(30)25-14-15(22)26-17(27-16(14)23)13-11-6-10(20)7-24-18(11)29(28-13)8-9-4-2-3-5-12(9)21/h2-7H,8H2,1H3,(H,25,30)(H4,22,23,26,27)
• InChI Key: QZFHIXARHDBPBY-UHFFFAOYSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Vericiguat (BAY1021189) is a potent, orally available and soluble guanylate cyclase stimulator.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 53.52; H, 3.78; F, 8.91; N, 26.28; O, 7.50
• Exact Mass: 426.1364
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The stimulation of sGC by vericiguat (24) was examined with a recombinant CHO cell line overexpressing rat sGC. 24 stimulated the sGC reporter cell line concentration dependently, with an EC50 of 1005 ± 145 nM. In the presence of the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) (30 and 100 nM), the EC50 value shifted to 39.0 ± 5.1 and 10.6 ± 1.7 nM, respectively. In the presence of ODQ, pretreatment of the sGC reporter cell line with 10 μM ODQ for 3 h resulted in a significantly reduced efficacy of 24, with an EC50 of 256 ± 40 nM being observed.; Reference: J Med Chem. 2017 Jun 22;60(12):5146-5161. http://dx.doi.org/10.1021/acs.jmedchem.7b00449
• In Vivo Activity: Chronic oral treatment with 3 or 10 mg/kg vericiguat (24) qd resulted in a significant attenuation of blood pressure increase during the course of the study. However, the overall rise of blood pressure increase was not halted in the 3 and 10 mg/kg treatment groups (Figure 4). With respect to kidney damage, 24 treatment at 3 or 10 mg/kg led to a significant reduction in kidney injury molecule Kim-1 and osteopontin expression which are used as biomarkers for renal injury and dysfunction (data not shown). In addition, proteinuria was significantly and dose dependently decreased in the treatment groups, also suggesting a functional improvement of the kidneys (Figure 6). Treatment with 24 resulted in a significant and dose-dependent increase in survival rates. In the 3 and 10 mg/kg qd treatment groups, the rat survival rate was 70% and 90%, respectively, at the study end. In contrast, the survival rate in the placebo group was only 25% after 21 days (Figure 7).; Reference: J Med Chem. 2017 Jun 22;60(12):5146-5161. http://dx.doi.org/10.1021/acs.jmedchem.7b00449
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).