Pharmacodynamic and pharmacokinetic effects of S086, a novel angiotensin receptor neprilysin inhibitor

Sun, Jing-Chao; Xu, Wenjie; Hua, Huaijie; Xiao, Ying; Chen, Xiaoyan; Gao, Zhiwei; Li, Song; Xie, Jing; Du, Frank; Sun, Guiju

doi:10.1016/j.biopha.2020.110410

Cited by 9 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first ARNi drug, LCZ696, has been reported to have significant antihypertensive effects, particularly in patients with salt-sensitive hypertension, and its clinical efficacy in reducing blood pressure is significantly better than that of Olmesartan, an angiotensin receptor blocker (ARB) ( 12 ). S086, a new generation of ARNi product developed by Salubris, has validated anti-heart failure effects in preclinical MI (Myocardial Infarction) chronic heart failure models and completed phase 1 clinical trial ( 17 , 18 ). We investigated the antihypertensive effect of S086 compared to LCZ696 using the DSS rat model of hypertension and explored the diuretic and natriuretic effects of ARNi drugs.…”

Section: Discussionmentioning

confidence: 99%

“…S086 has been proven to have comparable efficacy to LCZ696 in rat and dog myocardial infarction models. Both S086 and LCZ696 improved the left ventricular ejection fraction and myocardial fibrosis, and do not have a significant impact on hemodynamics ( 17 ). The phase I clinical trial for S086 in healthy volunteers indicated a dose-dependent pharmacokinetic profile (C max and AUC) and pharmacodynamic effect (mean diastolic and systolic blood pressure).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model

Sun,

Xiao,

et al. 2024

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

IntroductionAngiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension.MethodsDahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696.Results and discussionThe study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model

Sun,

Xiao,

et al. 2024

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The first ARNi drug, LCZ696, has been reported to have significant antihypertensive effects, particularly in patients with salt-sensitive hypertension, and its clinical efficacy in reducing blood pressure is significantly better than that of olmesartan, an angiotensin receptor blocker (ARB) (Wang, Tan, et al, 2017). S086, a new generation of ARNi product developed by Salubris, has validated anti-heart failure effects in preclinical MI chronic heart failure models and completed phase 1 clinical trial (Sun, Xu, et al, 2020;. We investigated the antihypertensive effect of S086 compared to LCZ696 using the DSS rat model of hypertension and explored the diuretic and natriuretic effects of ARNi drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Although the antihypertensive effect of the NEP inhibitor is relatively moderate, it is still stronger than that of the separate dose of EXP3174. Secondly, sacubitril increases the exposure level of EXP3174, resulting in a higher exposure after administering an equimolar dose of S086 (Sun, Xu, et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…S086 has been proven to have comparable efficacy to LCZ696 in rat and dog myocardial infarction models. Both S086 and LCZ696 improved the left ventricular ejection fraction and myocardial fibrosis, and do not have a significant impact on hemodynamics (Sun, Xu, et al, 2020). The phase I clinical trial for S086 in healthy volunteers indicated a dose-dependent PK profile and PD effect.…”

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Anti-hypertensive Effect of a Novel Angiotensin II Receptor Neprilysin Inhibitor (ARNi) -S086 in DSS rat model

Sun¹,

Yan²,

Xiao³

et al. 2023

Preprint

View full text Add to dashboard Cite

Background and Purpose: Angiotensin receptor-NEP inhibitor (ARNi), which is consisting of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has been proven safe and effective for treating hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension. Rat hypertension model and telemetry system were used in our study to investigate circadian rhythm of rat blood pressure and evaluate the anti-hypertensive efficacy of S086. Experimental Approach: Dahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were used in this research. Key Results: Our findings revealed the circadian rhythm of DSS rat blood pressure was opposite to that of humans, with high blood pressure occurring during the night. Oral administration of S086 dose-dependently lowered the blood pressure and exhibited better efficacy than LCZ696, particularly 16-24h after dosing. No significant changes were observed on water consumption, natriuresis and diuresis among all high salt groups. Conclusion: This paper demonstrates the ability of anti-hypertensive effect of S086 in preclinic and supports the product to conduct phase 2/3 clinical trial. Implications: This study reveals circadian rhythm of DSS rat blood pressure and provides the anti-hypertensive efficacy of S086 to support the further clinical study.

show abstract

Protective effect of novel angiotensin receptor neprilysin inhibitor S086 on target organ injury in spontaneously hypertensive rats

Xiao,

Zhou,

Sun

et al. 2024

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Pharmacodynamic and pharmacokinetic effects of S086, a novel angiotensin receptor neprilysin inhibitor

Cited by 9 publications

References 20 publications

Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model

Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model

Anti-hypertensive Effect of a Novel Angiotensin II Receptor Neprilysin Inhibitor (ARNi) -S086 in DSS rat model

Protective effect of novel angiotensin receptor neprilysin inhibitor S086 on target organ injury in spontaneously hypertensive rats

Contact Info

Product

Resources

About