vericiguat Property

Boiling point:

535.9±50.0 °C(Predicted)

Density 

1.63±0.1 g/cm3(Predicted)

solubility 

DMSO:60.0(Max Conc. mg/mL);140.7(Max Conc. mM)

form 

A solid

pka

10.61±0.70(Predicted)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H311Toxic in contact with skin

H331Toxic if inhaled

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P310Immediately call a POISON CENTER or doctor/physician.

P330Rinse mouth.

P361Remove/Take off immediately all contaminated clothing.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

vericiguat Chemical Properties,Usage,Production

Description

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.

Uses

Vericiguat is a novel oral soluble guanylate cyclase (sGC) stimulator that enhances the cyclic guanosine monophosphate (GMP) production pathway, by directly stimulating soluble guanylate cyclase activity, as well as sensitizing soluble guanylate cyclase to endogenous NO. It was initially developed for potential to reduce mortality and morbidity associated with chronic heart failure with reduced ejection fraction.

Uses

Vericiguat is used on targeting cyclic guanosine monophosphate in the treatment of heart failure.

Definition

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.

Clinical Use

Vericiguat was advanced to clinical evaluation, as an oral therapy for chronic heart failure, either with reduced ejection fraction (HFrEF), or preserved EF (HFpEF). In mid-June 2020 Merck announced that the FDA had granted priority review status to vericiguat and based on this. The FDA approved vericiguat in January 2021, to reduce the risk of cardiovascular death, heart failure re-hospitalisation, or the requirement for outpatient intravenous diuretics, in patients with symptomatic chronic heart failure and ejection fraction less than 45%. This approval was based on efficacy data arising from the Phase 3 trial NCT02861534 (a.k.a. the VICTORIA trial).