Vericiguat (BAY1021189) is a potent and orally available guanylate cyclase stimulator.

Vericiguat inhibits the U46619-induced contractions of porcine coronary artery rings concentration-dependently (IC50: 956 nM). Vericiguat inhibits phenylephrine-induced contractions of rabbit saphenous artery rings, rabbit aortic rings, and canine femoral vein rings concentration-dependently (IC50: 798, 692, and 3072 nM, respectively). Vericiguat (0.01 μM to 100 μM) stimulates recombinant sGC concentration-dependently, by 1.7-fold to 57.6-fold. When combined with the NO donor diethylamine/nitric oxide complex, Vericiguat and DEA/NO have a synergistic effect on the enzyme activity over a wide range of concentrations. At the highest concentrations of Vericiguat (100 μM) and DEA/NO (100 nM), the specific activity of sGC is 341.6-fold above baseline. Vericiguat stimulates the sGC reporter cell line concentration-dependently (EC50: 1005±145 nM) [1].

Vericiguat causes a significant and dose-dependent increase in survival rates. Chronic oral treatment with Vericiguat (3 or 10 mg/kg, q.d.) results in a significant attenuation of blood pressure increase during the course of the study. Vericiguat (3 or 10 mg/kg) treatment leads to a significant reduction in kidney injury molecule Kim-1 and osteopontin expression which are used as biomarkers for renal injury and dysfunction. In the 3 and 10 mg/kg q.d. treatment groups, the rat survival rate is 70% and 90%, respectively, at the study end [1].