醛固酮合酶抑制剂治疗 CKD-猫眼课题宝

醛固酮合酶抑制剂治疗 CKD

批准号：

9138137

负责人：

Bert J. W. M. Oehlen

金额：

$61.09万

依托单位：

ANGION BIOMEDICA CORPORATION

依托单位国家：

美国

项目类别：

财政年份：

2013

资助国家：

美国

项目状态：

已结题

起止时间：

2013-06-20 至 2018-03-31

来源：

https://reporter.nih.gov/project-details/9138137

关键词：

Aldosterone Ames Assay Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Animal Model Animals Applications Grants CYP11B2 gene Canis familiaris Cardiovascular system Chromosome abnormality Chronic Kidney Failure Clinical Clinical Management Cytochrome P450 Development Disease Progression Disease model Dose Drug Interactions Drug Kinetics Enzyme Inhibition Enzymes Female Functional disorder Grant Hepatocyte Human In Vitro Intravenous Ion Channel Kidney Kidney Diseases Kilogram Lead Liver Microsomes Metabolism Modeling Mus Nephrectomy Neurologic Oral P-Glycoprotein Pathway interactions Patients Peptidyl-Dipeptidase A Pharmaceutical Preparations Pharmacodynamics Pharmacology Phenotype Physiology Play Production Rattus Reaction Refractory Regimen Renin-Angiotensin-Aldosterone System Resistance Role Safety Sampling Series Toxicology Work aged analytical method base clinically significant combat design diabetic in vitro Assay in vivo Model inhibitor/antagonist male method development micronucleus patient population pre-clinical public health relevance receptor respiratory salt sensitive small molecule inhibitor standard of care success

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中文摘要

翻译

描述(申请人提供)：肾素-血管紧张素-醛固酮系统(RAAS)在肾脏生理学中起着关键作用。血管紧张素转换酶(ACE)或血管紧张素受体阻滞剂(ARB)是治疗慢性肾脏疾病(CKD)等肾脏疾病的主要药物。尽管ACE抑制或ARB治疗最初取得成功，但患者往往对RAAS抑制剂产生耐药性。“醛固酮突破”现象的临床意义日益为人们所认识。对抗这一突破的一种方法是抑制负责产生醛固酮的酶：醛固酮合成酶。Angion已经发现了一种新的专有的非类固醇小分子醛固酮合成酶抑制剂，该药在CKD的临床前体内模型中显示出抗纤维化的作用。我们建议开展临床前开发活动，争取将我们的先导化合物提名为CKD的IND Track。

英文摘要

DESCRIPTION (provided by applicant): The renin-angiotensin-aldosterone system (RAAS) plays a critical role in renal physiology. Inhibitors of angiotensin-converting enzyme (ACE) or angiotensin receptor blockers (ARB) are the mainstay in the clinical management of renal disorders such as chronic kidney disease (CKD). Despite initial success of ACE inhibition or ARB therapy, patients often acquire resistance to RAAS inhibitors. The clinical significance of the phenomenon of "aldosterone breakthrough" is increasingly recognized. One approach to combat this breakthrough is to inhibit the enzyme responsible for aldosterone production: aldosterone synthase. Angion has identified a new proprietary non-steroidal small molecule inhibitor of aldosterone synthase, which shows anti-fibrotic effects in preclinical in vivo models f CKD. We propose to conduct preclinical development activities towards an IND track nomination of our lead compound for CKD.

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