Vericiguat (BAY1021189)
(Synonyms: 维利西呱; BAY1021189) 目录号 : GC32472
Vericiguat (BAY1021189)是一种口服可溶性鸟苷酸环化酶（sGC）激动剂，可抑制乳腺癌耐药蛋白（IC50=20µM）及OATP1B1/1B3（IC50分别约为16µM和30µM）。
Cas No.:1350653-20-1
Sample solution is provided at 25 µL, 10mM.
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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.
Vericiguat (BAY1021189)是一种口服可溶性鸟苷酸环化酶（sGC）激动剂，可抑制乳腺癌耐药蛋白（IC50=20µM）及OATP1B1/1B3（IC50分别约为16µM和30µM）[1]。Vericiguat能以浓度依赖性方式抑制苯肾上腺素诱导的兔隐动脉环、兔主动脉环及犬股静脉环收缩，IC50值分别为798nM、692nM和3072nM[2]。Vericiguat对硝酸酯耐药的兔隐动脉环产生舒张作用（IC50=5.8nM）[3]。Vericiguat广泛应用于心血管舒张与收缩功能研究[4]。
在体外，1μM浓度的Vericiguat处理24小时可阻止高糖环境下人平滑肌细胞的cGMP生成障碍及血管舒张功能受损[5]。350μg/L的Vericiguat预处理5分钟能直接抑制人离体血小板活化与聚集，阻断凝血酶或胶原诱导的ATP释放，并减弱凝血酶刺激的p-选择素暴露[6]。处理3小时后，500nM浓度的Vericiguat能促进破骨细胞（OC）分化，而8μM浓度的Vericiguat抑制OC分化[7]。
在体内，连续28天的Vericiguat 处理（10mg/kg/day；p.o.）可改善心肌梗死（MI）后C57/BL6小鼠的心功能障碍并缩小梗死面积[8]。灌胃给药Vericiguat（3mg/kg）3小时能增强猪缺血/再灌注模型中梗死区血管分布，抑制促炎细胞浸润并减少胶原沉积[9]。Vericiguat经口服给药（3mg/kg/day）14天可抑制雄性C57Bl/6J小鼠中的心肌氧化应激，显著改善血管紧张素II诱导的左心室肥厚与纤维化[10]。
| Cell experiment [1]: | |
Cell lines | Human smooth muscle cells |
Preparation Method | Human smooth muscle cells (HVSMCs) were placed in 6-well plates. When the cell confluence reaches 60% to 70%, replace the medium with serum-free medium. Culture was carried out using SmGM-2 smooth muscle cell growth medium. All experiments were conducted using 3-6 generations of cell cultures. After 24 hours, the cells were treated under the following three different conditions: normal glucose (5.5 mM D-glucose and 24.5mM L-glucose), high glucose (30mM d-glucose), or high glucose+1μM vericiguat for 24 hours. The selection of high glucose concentration is based on the previous HVSMCs study, which indicated that 24-hour HG exposure does indeed induce vascular dysfunction, thereby providing a relevant model for evaluating therapeutic intervention measures. To serve as a osmotic pressure control, 24.5mM L-glucose was added to 5.5mM D-glucose in the normal glucose group. All groups were treated with sildenafil (1μM) and NO donor DETA NONOate (0.1μM). NO donors were given because the HVSCMs system lacked endothelial cells, and thus there was NO endogenous NO production. Sildenafil was added to increase the half-life of cGMP and facilitate the determination of originally unstable compounds. After incubation for 24 hours, the cells were isolated and lysed, and then used to measure cGMP and PKG activities. |
Reaction Conditions | 1μM; 24h |
Applications | Vericiguat can rescue cGMP production and sGC activity in a hyperglycemic environment within HVSMCs. |
| Animal experiment [2]: | |
Animal models | Male C57/BL6 mice |
Preparation Method | Male C57/BL6 mice (8-10 weeks old) all adapted in a controlled environment with regulated light/dark cycles (12 hours of light /12 hours of darkness), temperature and humidity. The mice were fed standard rodent feed and could freely drink water with a water quality of 1.0% sodium chloride. In order to simulate the real clinical situation, the ligation method of the left anterior descending artery (LAD) was adopted to establish the myocardial infarction (MI) model in mice. The mice were divided into four treatment groups: Sham, Sham+Vericiguat, MI and MI+Vericiguat. Before the operation, mice were anesthetized by intraperitoneal injection of pentobarbital sodium (50mg/kg). Tracheal intubation was performed on mice and respiratory support was provided. The MI group (n=20) and the MI+Vericiguat group (n=20) underwent left thoracotomy and ligation of the LAD with 7-0 silk thread. The success of vascular occlusion was verified by the immediate whitening of the LAD perfusion area and the changes in dynamic electrocardiogram. Suture the chest cavity and skin with 5-0 silk thread. Similar surgeries were performed in the Sham group (n=20) and the Sham+ Vericiguat group (n=20), but LAD was not ligated. Vericiguat treatment (p.o.) was initiated 12 hours after MI and lasted for 28 days at a dose of 10mg/kg/ day. Penicillin (200,000 IU) was injected intramuscularly every day within one week after the operation. All surgeries and subsequent analyses were performed blinding. |
Dosage form | 10mg/kg/day for 28 days; p.o. |
Applications | Vericiguat treatment alleviated cardiac dysfunction and infarction area after myocardial infarction in mice. |
References: | |
| Cas No. | 1350653-20-1 | SDF | |
| 别名 | 维利西呱; BAY1021189 | ||
| Canonical SMILES | O=C(OC)NC1=C(N)N=C(C2=NN(CC3=CC=CC=C3F)C4=NC=C(F)C=C42)N=C1N | ||
| 分子式 | C19H16F2N8O2 | 分子量 | 426.38 |
| 溶解度 | DMSO : 60 mg/mL (140.72 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3453 mL | 11.7266 mL | 23.4533 mL |
| 5 mM | 0.4691 mL | 2.3453 mL | 4.6907 mL |
| 10 mM | 0.2345 mL | 1.1727 mL | 2.3453 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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