Vericiguat (BAY1021189) is an oral soluble guanylate cyclase (sGC) stimulant and an inhibitor of breast cancer resistance protein (IC50 = 20µM) as well as OATP1B1 and 1B3 (approximate IC50 of 16 and 30µM, respectively)[1]. Vericiguat inhibited phenylephrine-induced contractions of rabbit saphenous artery rings, rabbit aortic rings, and canine femoral vein rings in a concentration-dependent manner, with IC50 values of 798, 692, and 3072nM, respectively[2]. Vericiguat can relax the isolated cryptoarterial rings of rabbits that are tolerant to nitrate, with an IC50 value of 5.8nM[3]. Vericiguat has been widely used in the research of cardiovascular diastolic and systolic studies[4].
In vitro, Vericiguat treatment at a concentration of 1μM for 24 hours can prevent impaired cGMP production and vasodilation mediated by high glucose in human smooth muscle cells[5]. Pretreatment with Vericiguat at a concentration of 350μg/L for 5 minutes directly inhibited platelet activation and aggregation in human isolated platelets, suppressed ATP release induced by thrombin or collagen, and weakened p-selectin exposure stimulated by thrombin[6]. After 3 hours of treatment, Vericiguat can promote the differentiation of osteoclasts (OC) at a concentration of 500nM, and inhibit the differentiation of OC at a concentration of 8μM[7].
In vivo, Vericiguat treatment (10mg/kg/day; p.o.) for 28 days alleviated cardiac dysfunction and infarction area after myocardial infarction (MI) in C57/BL6 mice[8]. Intragastric administration of 3mg/kg Vericiguat for 3 hours enhanced the vascular distribution in the infarcted area of pig model of ischemia/reperfusion, inhibited pro-inflammatory cells, and reduced collagen deposition[9]. Vericiguat (3mg/kg/day) administered orally for 14 days can inhibit myocardial oxidative stress, and significantly improve angiotensin II-induced left ventricular hypertrophy and fibrosis in male C57Bl/6J mice[10].
References:
[1] Boettcher M, Gerisch M, Lobmeyer M, et al. Metabolism and pharmacokinetic drug–drug interaction profile of vericiguat, a soluble guanylate cyclase stimulator: Results from Preclinical and Phase I Healthy Volunteer Studies[J]. Clinical pharmacokinetics, 2020, 59: 1407-1418.
[2] Markham A, Duggan S. Vericiguat: first approval[J]. Drugs, 2021, 81(6): 721-726.
[3] Fritsch A, Meyer M, Blaustein R O, et al. Clinical pharmacokinetic and pharmacodynamic profile of vericiguat[J]. Clinical Pharmacokinetics, 2024, 63(6): 751-771.
[4] Follmann M, Ackerstaff J, Redlich G, et al. Discovery of the soluble guanylate cyclase stimulator vericiguat (BAY 1021189) for the treatment of chronic heart failure[J]. Journal of medicinal chemistry, 2017, 60(12): 5146-5161.
[5] Polhemus D, Almodiel D, Harb T, et al. Vericiguat prevents high glucose-mediated impaired vascular smooth muscle cGMP production and vasorelaxation[J]. Scientific Reports, 2025, 15(1): 4939.
[6] Zhou W, Zhou L, Qi Z, et al. The soluble guanylate cyclase (sGC) stimulator vericiguat inhibits platelet activation and thrombosis[J]. European Journal of Pharmacology, 2025: 177670.
[7] Sun K, Kong F, Lin F, et al. Vericiguat modulates osteoclast differentiation and bone resorption via a balance between VASP and NF‐κB pathways[J]. Mediators of Inflammation, 2022, 2022(1): 1625290.
[8] Chen T, Kong B, Shuai W, et al. Vericiguat alleviates ventricular remodeling and arrhythmias in mouse models of myocardial infarction via CaMKII signaling[J]. Life Sciences, 2023, 334: 122184.
[9] Zhu W, Ben Y, Shen Y, et al. Vericiguat protects against cardiac damage in a pig model of ischemia/reperfusion[J]. Plos one, 2023, 18(12): e0295566.
[10] Harada T, Kondo H, Nakamura K, et al. Soluble Guanylate Cyclase Stimulator Vericiguat Attenuates Angiotensin II-Induced Oxidative Stress and Cardiac Remodeling[J]. Circulation Journal, 2025: CJ-24-0659.