SAR-407899(SAR-407899) - 药物靶点：ROCK_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

ROCK

作用机制

ROCK 抑制剂(Rho-相关激酶抑制剂)

治疗领域

免疫系统疾病神经系统疾病心血管疾病+ [6]

在研适应症-

非在研适应症

稳定型心绞痛慢性肾病勃起功能障碍+ [2]

原研机构

Sanofi-Aventis U.S. LLC

在研机构-

非在研机构

Sanofi

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C14H16N2O2

InChIKeyIPEXHQGMTHOKQV-UHFFFAOYSA-N

CAS号923359-38-0

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关联

6

项与 SAR-407899 相关的临床试验

EUCTR2016-000629-38-NL / Not yet recruiting临床2期

A randomized, double-blind, placebo-controlled parallel arm dose titration study to assess the effects of SAR407899 in patients with microvascular angina and/or persistent stable angina despite angiographically successful elective percutaneous coronary intervention (PCI)

开始日期2017-10-30

申办/合作机构

Sanofi-Aventis Recherche et Développement SA

NCT03236311 / Terminated临床2期

A Randomized, Double-blind, Placebo-controlled Parallel Arm Dose Titration Study to Assess the Effects of SAR407899 in Patients With Microvascular Angina (MVA) and/or Persistent Stable Angina Despite Angiographically Successful Percutaneous Coronary Intervention (PCI)

Primary Objective:
To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI).
Secondary Objectives:
To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation scale (SAQ-PL) in participants with MVA and/or persistent stable angina despite angiographically successful PCI.
To assess the safety of SAR407899 in participants with MVA and/or persistent stable angina despite angiographically successful PCI with a focus on identified risks such as hypotension and orthostatic hypotension.
To assess SAR407899 plasma concentrations in MVA participants and/or persistent stable angina despite angiographically successful PCI.

开始日期2017-10-12

申办/合作机构

Sanofi

NCT01485900 / Completed临床1期

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Hemodynamics of Ascending Repeated Oral Doses of SAR407899A in Patients With Moderate Chronic Kidney Disease on Stable Angiotensin Converting Enzyme-inhibitor (ACE-I) Treatment

Primary Objective:
To assess the tolerability and safety of repeated oral ascending doses of SAR407899A in patients with moderate chronic kidney disease (CKD) on stable angiotensin converting enzyme-inhibitor (ACE-I)
Secondary Objectives:
To assess in patients with moderate CKD the effect of concomitant multiple dose of SAR407899A and ACE-Is on office and 24-hr ambulatory blood pressure and heart rate
The effect of repeated multiple doses of SAR407899A on the pharmacodynamic response to ACE-Is (AcSDKP)
The pharmacokinetic profile of repeated oral administration of SAR407899A during co-administration of ACE-Is

开始日期2011-11-01

申办/合作机构

Sanofi

100 项与 SAR-407899 相关的临床结果

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100 项与 SAR-407899 相关的转化医学

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100 项与 SAR-407899 相关的专利（医药）

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7

项与 SAR-407899 相关的文献（医药）

2018-10-01·Transplant Immunology4区 · 医学

Screening RhoA/ROCK inhibitors for the ability to prevent chronic rejection of mouse cardiac allografts

4区 · 医学

Article

作者: Wenhao Chen ; Rafik M. Ghobrial ; Malgorzata Kloc ; Wei Chen ; Xian C. Li ; Song Chen

BACKGROUNDChronic rejection of transplanted organs is a major obstacle in organ transplantation. The main symptoms of chronic rejection are vessel occlusion and tissue fibrosis. Macrophages play a crucial role in chronic rejection. We showed previously that RhoA deletion or RhoA/Rock inhibition using Y27632 inhibitor reorganizes macrophage actin cytoskeleton, prevents macrophage movement to the cardiac allografts, and abrogates chronic rejection in rodent models. Although besides Y27632 there are other RhoA/ROCK inhibitors available commercially, their efficacy in inhibition of chronic rejection remains unknown.METHODSWe screened four RhoA/Rock inhibitors for their ability to inhibit chronic rejection of BALB/c [H-2d] mouse cardiac allografts heterotopically transplanted into C57BL/6 [H-2b] recipients. We also tested the effect of inhibitors on macrophages in vitro.RESULTSWe found that out of four tested compounds, the Fasudil and Azaindole, inhibited vessel occlusion, tissue fibrosis, decreased M2 macrophage infiltration and abrogated chronic rejection of mouse cardiac allografts. The remaining inhibitors, SAR-407899 and SLX-2119, decreased only tissue fibrosis, and were ineffective or only slightly effective in inhibiting vessel occlusion. We also found that Azaindole and Fasudil affected actin cytoskeleton and protein expression in mouse peritoneal macrophages CONCLUSION: Results of these studies might help in development of anti-chronic rejection therapy for clinical use.

2015-01-01·World Journal of Cardiology

End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899

Article

作者: Löhn, Matthias ; Hofmeister, Armin ; Kadereit, Dieter ; Plettenburg, Oliver ; Ruetten, Hartmut ; Kannt, Aimo ; Ivashchenko, Yuri ; Kohlmann, Markus ; Schulte, Anke ; Schiffer, Alexander ; Monecke, Peter

AIMTo compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme (ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage.METHODSLong-term pharmacological characte-rization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition (LNAME) and the other is insensitive [deoxycorticosterone acetate (DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension.RESULTSLong term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calcium channel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension.CONCLUSIONRho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.

2012-12-01·Journal of Translational Medicine2区 · 医学

Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa

2区 · 医学

ArticleOA

作者: Fabio Guagnini ; Tiziano Croci ; Marco Grasso ; Mara Ferazzini ; Salvatore Blanco

BACKGROUNDRhoA-Rho kinase complex contributes to keep the cavernosus smooth muscle contracted and its inhibition is considered a potential strategy for the therapy of erectile dysfunction (ED).METHODSWe compared the effects of SAR407899, the Rho-kinase inhibitor Y-27632 and the PDE5 inhibitor sildenafil for their ability to relax corpus cavernosum strips contracted with phenylephrine in healthy and diabetic animals. Strips were obtained from WKY, spontaneous hypertensive (SHR), control CD, and diabetic CD rats, humans, control and diabetic rabbits. Diabetes was induced by streptozotocin or alloxan injection. In vivo penile erection (length) induced by drugs was measured in conscious rabbits.RESULTSSAR407899 dose-dependently relaxed the pre-contracted corpora cavernosa in all species, with similar potency and efficacy in healthy vs diabetic rats, WKY vs SHR rats, healthy vs diabetic rabbits (IC(50) range from 0.05 to 0.29 μM, Emax range 89 to 97%). In the presence of the NO-synthase (NOS) inhibitor, L-NAME, the SAR407899 response did not decrease in any of the species or experimental conditions. The effect was confirmed in human strips where sildenafil was significantly less potent and effective, with IC50 respectively 0.13 and 0.51 μM; Emax 92 and 43%. Unlike SAR407899, the potency and efficacy of sildenafil and Y27632 were significantly reduced by diabetes and L-NAME. In vivo, SAR407899 dose-dependently induced rabbit penile erection, with greater potency and longer duration of action than sildenafil. Sildenafil, but not SAR407899, was less effective in alloxan-induced diabetes.CONCLUSIONThe induction of penile erection by SAR407899, unlike that by sildenafil, is largely independent of e-NO activity. This suggests its use in erectile dysfunction for diabetic and hypertensive patients where e-NO activity is impaired.

100 项与 SAR-407899 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
稳定型心绞痛	临床2期	韩国	Sanofi	2017-10-12
稳定型心绞痛	临床2期	瑞典	Sanofi	2017-10-12
稳定型心绞痛	临床2期	美国	Sanofi	2017-10-12
稳定型心绞痛	临床2期	荷兰	Sanofi	2017-10-12
甲羟戊酸激酶缺乏症	临床2期	韩国	Sanofi	2017-10-12
甲羟戊酸激酶缺乏症	临床2期	荷兰	Sanofi	2017-10-12
甲羟戊酸激酶缺乏症	临床2期	丹麦	Sanofi	2017-10-12
甲羟戊酸激酶缺乏症	临床2期	美国	Sanofi	2017-10-12
甲羟戊酸激酶缺乏症	临床2期	瑞典	Sanofi	2017-10-12
勃起功能障碍	临床2期	法国	Sanofi	2009-05-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03236311 (CTgov)	临床2期	微血管心绞痛 \| 甲羟戊酸激酶缺乏症 \| 稳定型心绞痛	10	82Rubidium+13N-ammonia+Regadenoson+Adenosine (Placebo)	憲窪壓鏇鏇網鹹憲製願(鹹膚窪壓壓選積鬱艱鹹) = 鹽夢糧壓蓋簾簾顧壓構糧餘願壓蓋壓糧醖窪構 (醖繭醖醖蓋獵製壓餘壓, 製觸積醖衊鬱艱積製築 ~ 淵窪願壓築膚壓壓範顧) 更多	-	2019-07-11
				82Rubidium+SAR407899+13N-ammonia+Regadenoson+Adenosine (SAR407899)	憲窪壓鏇鏇網鹹憲製願(鹹膚窪壓壓選積鬱艱鹹) = 範餘網鹽築壓製夢憲鏇糧餘願壓蓋壓糧醖窪構 (醖繭醖醖蓋獵製壓餘壓, 築淵壓蓋積網製網鏇衊 ~ 夢顧觸遞鑰顧襯積醖齋) 更多