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Aldosterone Synthase Inhibitor for CKD

醛固酮合酶抑制剂治疗 CKD

基本信息

批准号：
9245691
负责人：
Bert J. W. M. Oehlen
金额：
$ 70.91万
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
起止时间：
2013-06-20 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9245691
关键词：
Aldosterone Ames Assay Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Animal Model Animals Applications Grants Biological Assay CYP11B2 gene Canis familiaris Cardiovascular system Chromosome abnormality Chronic Kidney Failure Clinical Management Cytochrome P450 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 Study Phenotype Physiology Play Production Rattus Reaction Refractory Regimen Renin-Angiotensin-Aldosterone System Resistance Role Safety Sampling Series Toxicology Work aged analytical method base clinical development clinically significant combat design diabetic drug development efficacy study in vivo Model inhibitor/antagonist male micronucleus patient population pre-clinical preclinical development public health relevance receptor respiratory salt sensitive small molecule inhibitor standard of care success

项目摘要

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.

描述（由申请人提供）：肾素-血管紧张素-醛固酮系统（RAAS）在肾脏生理学中起关键作用。血管紧张素转换酶（ACE）抑制剂或血管紧张素受体阻滞剂（ARB）是慢性肾脏疾病（CKD）等肾脏疾病临床治疗的主要药物。尽管ACE抑制剂或ARB治疗取得了初步成功，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被认识。对抗这一突破的一种方法是抑制负责醛固酮产生的酶：醛固酮合酶。Angion已经确定了一种新的专有非甾体小分子醛固酮合成酶抑制剂，该抑制剂在慢性肾脏病的临床前体内模型中显示出抗纤维化作用。我们建议开展临床前开发活动，以获得CKD先导化合物的IND跟踪提名。