Vericiguat

Vericiguat (BAY1021189) is a potent, orally available and soluble guanylate cyclase stimulator. In Vitro: 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 (DEA/NO), vericiguat and DEA/NO have a synergistic effect on the enzyme activity over a wide range of concentrations. At 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, with an EC₅₀ of 1005±145 nM. Vericiguat inhibits phenylephrine-induced contractions of rabbit saphenous artery rings, rabbit aortic rings, and canine femoral vein rings concentration dependently, with IC₅₀ values of 798, 692, and 3072 nM, respectively. Vericiguat inhibits the U46619-induced contractions of porcine coronary artery rings concentration dependently, with an IC₅₀ of 956 nM^[1]. In Vivo: Vericiguat (compound 24) (oral administration; 3 mg/kg, 10 mg/kg; once daily; 21 days) maintains heart and kidney function in a model of hypertension-induced end-organ damage in L-NAME-treated renin transgenic rats. Additionally,Vericiguat-treated group substantially reduces overall mortality when compared to the control group^[1].