BI 685509 (Avenciguat) is a potent, selective and orally bioavailable soluble guanylate cyclase (sGC) activator, increases cGMP in human and rat platelet-rich plasma treated with ODQ with EC50 of 467 nM and 304 nM, respectively.
BI 685509 increased cGMP production with an EC50 of 9.29, 3.52, 4.69, 8.65, and 5.54 nM against the mouse, rat, dog, cynomolgus monkey, and human α2/β1 enzyme, respectively, compared with an EC50 of 6.81 nM against the human α1/β1 enzyme.
In conscious telemetry-instrumented rats, BI 685509 did not effect mean arterial pressure (MAP) or heart rate (HR) at 3 and 10 mg/kg (p.o.), whereas 30 mg/kg decreased MAP and increased HR.
BI 685509 at supratherapeutic doses (60 or 100 mg/kg po, qd, 10 days) attenuated MAP and HR responses to a single 100 mg/kg challenge.
BI 685509 (1, 3, 10, 30 mg/kg/day qd) co-administered with enalapril (3 mg/kg/day) dose-dependently reduced proteinuria and incidence of glomerular sclerosis in the ZSF1 rat model.
BI 685509 dose-dependently reduced tubulointerstitial fibrosis in the 7-day rat UUO model.