Vericiguat enhances the activity of recombinant soluble guanylate cyclase (sGC) in a concentration-dependent manner, ranging from a 1.7-fold to a 57.6-fold increase. In combination with the nitric oxide donor diethylamine/nitric oxide complex (DEA/NO), Vericiguat and DEA/NO exhibit a synergistic effect on sGC activity across various concentrations. At the highest concentrations tested (100 μM for Vericiguat and 100 nM for DEA/NO), sGC activity is elevated 341.6-fold above the baseline. Vericiguat also concentration-dependently activates an sGC reporter cell line, with an EC50 of 1005±145 nM. It concentration-dependently inhibits phenylephrine-induced contractions in rabbit saphenous artery rings, rabbit aortic rings, and canine femoral vein rings, with IC50 values of 798, 692, and 3072 nM, respectively. Moreover, Vericiguat concentration-dependently inhibits U46619-induced contractions in porcine coronary artery rings, with an IC50 of 956 nM[1].
体内研究
With oral administration at doses of 3 mg/kg and 10 mg/kg once daily for 21 days, Vericiguat preserves heart and kidney function in a model of hypertension-induced end-organ damage in L-NAME-treated renin transgenic rats. Importantly, the Vericiguat-treated group exhibits a significant reduction in overall mortality compared to the control group[1].
体外研究
Vericiguat enhances the activity of recombinant soluble guanylate cyclase (sGC) in a concentration-dependent manner, ranging from a 1.7-fold to a 57.6-fold increase. In combination with the nitric oxide donor diethylamine/nitric oxide complex (DEA/NO), Vericiguat and DEA/NO exhibit a synergistic effect on sGC activity across various concentrations. At the highest concentrations tested (100 μM for Vericiguat and 100 nM for DEA/NO), sGC activity is elevated 341.6-fold above the baseline. Vericiguat also concentration-dependently activates an sGC reporter cell line, with an EC50 of 1005±145 nM. It concentration-dependently inhibits phenylephrine-induced contractions in rabbit saphenous artery rings, rabbit aortic rings, and canine femoral vein rings, with IC50 values of 798, 692, and 3072 nM, respectively. Moreover, Vericiguat concentration-dependently inhibits U46619-induced contractions in porcine coronary artery rings, with an IC50 of 956 nM[1].
Vericiguat/维利西呱 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone marrow-derived monocyte-macrophage lineage (BMMs)
0-8 µM
24 hours
To evaluate the cytotoxicity of Vericiguat on BMMs, results showed no cytotoxicity within 0-8 μM
Mediators Inflamm. 2022 Jun 16;2022:1625290
Human aortic vascular smooth muscle cells (HVSMCs)
1 µM
24 hours
To test whether vericiguat reverses HG-mediated decreased sGC activity. Results showed that cGMP production and PKG activity were significantly impaired in HG cells without vericiguat but were comparable to NG when treated with vericiguat.
Sci Rep. 2025 Feb 10;15(1):4939
Bone marrow-derived monocyte-macrophage lineage (BMMs)
8 µM
6 days
To evaluate the effect of Vericiguat on osteoclast differentiation, results showed 8 μM concentration inhibited osteoclast differentiation
Mediators Inflamm. 2022 Jun 16;2022:1625290
Bone marrow-derived monocyte-macrophage lineage (BMMs)
500 nM
6 days
To evaluate the effect of Vericiguat on osteoclast differentiation, results showed 500 nM concentration promoted osteoclast differentiation
Mediators Inflamm. 2022 Jun 16;2022:1625290
Vericiguat/维利西呱 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague Dawley rats
Doxorubicin-induced cardiomyopathy model
Intragastric administration
1 mg/kg/day
Once daily for 8 weeks
Vericiguat effectively reversed DOX-induced cardiac remodelling and improved systolic function. Mechanistically, Vericiguat attenuated the inhibitory effects of DOX on the myocardial cGMP-PKG axis and nuclear factor erythroid 2-related factor 2 (Nrf2) protein, thereby alleviating oxidative stress and apoptosis.
ESC Heart Fail. 2025 Jun;12(3):1807-1817
Human
Heart failure patients
Oral
10 mg once daily
Once daily for 10.8 months
To evaluate the effect of Vericiguat in reducing the risk of cardiovascular death or heart failure hospitalization when added to standard therapy. Results showed a significant 10% reduction in the primary composite endpoint (cardiovascular death or first heart failure hospitalization).
ESC Heart Fail. 2024 Apr;11(2):628-636
Mice
Isolated mouse aortic rings
Organ chamber bath
105.5 μM
24 hours
To evaluate the effect of vericiguat on vascular relaxation in HG conditions. Results showed that ACh-mediated relaxation was impaired in HG but restored and even enhanced with vericiguat treatment.
Sci Rep. 2025 Feb 10;15(1):4939
Rats
Heart failure model
Oral
3 mg/kg
Once daily for 4 weeks
To evaluate the therapeutic effect of Vericiguat on heart failure, results showed significant improvement in cardiac function
To evaluate the therapeutic effects of Vericiguat on OVX-induced bone loss, results showed high-dose Vericiguat (10 μg/kg/day) significantly improved bone loss
Mediators Inflamm. 2022 Jun 16;2022:1625290
Human
Patients with heart failure
Oral
Target dose of 10 mg
Once daily, during the treatment period
To evaluate the effect of vericiguat on the primary composite endpoint of cardiovascular death or first hospitalization for HF in patients with heart failure. Results showed that vericiguat significantly reduced the risk of the primary composite endpoint in the NT-proBNP Q1-Q3 group (HR 0.78; 95% CI 0.69–0.88, P<0.001), but no significant difference was observed in the Q4 group (HR 1.15; 95% CI 0.99–1.34, P=0.070).
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