WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 319687
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).
MedKoo Cat#: 319687
Chemical Formula: C19H16F2N8O2
Exact Mass: 426.1364
Molecular Weight: 426.39
Elemental Analysis: C, 53.52; H, 3.78; F, 8.91; N, 26.28; O, 7.50
Synonym: BAY1021189; BAY 1021189; BAY-1021189; BAY10-21189; BAY-10-21189; BAY 10-21189; Vericiguat.
IUPAC/Chemical Name: methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate
InChi Key: QZFHIXARHDBPBY-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(OC)NC1=C(N)N=C(C2=NN(CC3=CC=CC=C3F)C4=NC=C(F)C=C42)N=C1N
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Vericiguat (BAY1021189) is a potent, orally available and soluble guanylate cyclase stimulator.|
|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|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 426.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Follmann M, Ackerstaff J, Redlich G, Wunder F, Lang D, Kern A, Fey P, Griebenow N, Kroh W, Becker-Pelster EM, Kretschmer A, Geiss V, Li V, Straub A, Mittendorf J, Jautelat R, Schirok H, Schlemmer KH, Lustig K, Gerisch M, Knorr A, Tinel H, Mondritzki T, Trübel H, Sandner P, Stasch JP. Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure. J Med Chem. 2017 Jun 22;60(12):5146-5161. doi: 10.1021/acs.jmedchem.7b00449. Epub 2017 Jun 12. PMID: 28557445.|
|In vivo protocol:||1. Follmann M, Ackerstaff J, Redlich G, Wunder F, Lang D, Kern A, Fey P, Griebenow N, Kroh W, Becker-Pelster EM, Kretschmer A, Geiss V, Li V, Straub A, Mittendorf J, Jautelat R, Schirok H, Schlemmer KH, Lustig K, Gerisch M, Knorr A, Tinel H, Mondritzki T, Trübel H, Sandner P, Stasch JP. Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure. J Med Chem. 2017 Jun 22;60(12):5146-5161. doi: 10.1021/acs.jmedchem.7b00449. Epub 2017 Jun 12. PMID: 28557445.|
1: Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Müller K, Roessig L, Pieske B; SOCRATES-REDUCED Investigators and Coordinators. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. JAMA. 2015 Dec 1;314(21):2251-62. doi: 10.1001/jama.2015.15734. PubMed PMID: 26547357.
2: Tschöpe C, Pieske B. [New therapy concepts for heart failure with preserved ejection fraction]. Herz. 2015 Apr;40(2):194-205. doi: 10.1007/s00059-015-4210-x. German. PubMed PMID: 25737289.
3: Stasch JP, Schlossmann J, Hocher B. Renal effects of soluble guanylate cyclase stimulators and activators: a review of the preclinical evidence. Curr Opin Pharmacol. 2015 Apr;21:95-104. doi: 10.1016/j.coph.2014.12.014. Epub 2015 Jan 31. Review. PubMed PMID: 25645316.
4: Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Müller K, Roessig L, Gheorghiade M; SOCRATES Investigators and Coordinators. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail. 2014 Sep;16(9):1026-38. doi: 10.1002/ejhf.135. Epub 2014 Jul 24. PubMed PMID: 25056511.
5: Stasch JP, Evgenov OV. Soluble guanylate cyclase stimulators in pulmonary hypertension. Handb Exp Pharmacol. 2013;218:279-313. doi: 10.1007/978-3-642-38664-0_12. Review. PubMed PMID: 24092345.