Vericiguat

Vericiguat is a novel oral soluble guanylate cyclase (sGC) stimulator.- Soluble guanylate cyclase (sGC) is an enzyme that is activated by nitric oxide (NO). The activation initiates a signaling cascade which converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). cGMP levels increase & protein kinase G (PKG) is activated, resulting in a decrease of intracellular free Ca++ -> vascular smooth muscle cell relaxation.- However, individuals with HF have reduced NO levels. Vericiguat, as a sGC stimulator, increases the enzymatic activity of sGC to generate cGMP independently of NO and enhances sGC sensitivity to endogenous NO.Vericiguat is the 2nd drug in this class and follows riociguat ADEMPAS, which has been approved for treating pulmonary arterial hypertension.SOCRATES-REDUCED was a phase II dose-finding trial of vericiguat in HF-rEF. The primary endpoint, change in NTproBNP over 12 weeks, was not statistically significant compared to placebo. A secondary exploratory analysis suggested a dose-response relationship in which higher doses of vericiguat were associated with greater reductions in NTproBNP levels.
ChEBI: Vericiguat is a pyrazolopyridine that is 5-fluoro-1H-pyrazolo[3,4-b]pyridine in which the amino hydrogen at position 1 has been substituted by a 2-fluorobenzyl group and the hydrogen at position 3 has been substituted by a 4,6-diamino-5-[(methoxycarbonyl)amino]pyrimidin-2-yl group. It is a soluble guanylate cyclase stimulator which is used for treatment of chronic heart failure. It has a role as a soluble guanylate cyclase activator, a vasodilator agent and an antihypertensive agent. It is an aminopyrimidine, a pyrazolopyridine, a carbamate ester and an organofluorine compound.