过氧化物酶体增殖物激活受体激动剂安全性研究进展  

Research progress in safety of PPAR agonists

作　　者：张琴 张陆勇[1,4] 江振洲[1,2,3] ZHANG Qin;ZHANG Luyong;JIANG Zhenzhou(New Drug Screening Center,China Pharmaceutical University,Nanjing Jiangsu 210009,China;Jiangsu Center for Pharmacodynamics Research and Evaluation,Nanjing Jiangsu 210009,China;Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education,China Pharmaceutical University,Nanjing Jiangsu 210009,China;Center for Drug Research and Development,Guangdong Pharmaceutical University,Guangzhou Guangdong 510006,China)

机构地区：[1]中国药科大学新药筛选中心,江苏南京210009 [2]中国药科大学江苏省药效研究与评价服务中心,江苏南京210009 [3]中国药科大学药物质量与安全预警教育部重点实验室,江苏南京210009 [4]广东药科大学新药研发中心,广东广州510006

出　　处：《中国药物警戒》2023年第8期950-955,共6页Chinese Journal of Pharmacovigilance

基　　金：双一流团队“药物安全预警关键技术研究创新团队”资助项目(CPU2018GY33);江苏省第“六大人才高峰”高层次人才选拔培养资助(SWYY-094);国家科技重大专项新药创制(2015ZX09501004-002-004);国家自然科学基金资助项目(81773827)。

摘　　要：过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPAR)是调控能量代谢、炎症反应、细胞发育和分化相关基因表达的重要核受体。其激动剂已被开发用于治疗糖尿病,血脂异常和动脉粥样硬化等代谢性疾病。PPAR激动剂的不良反应限制了其在临床上的使用以及新型PPAR激动剂的开发。本文对特异性PPAR激动剂相关的毒性类型和毒性机制进行了归纳整理,并介绍了临床试验中双重PPAR激动剂和泛PPAR激动剂的不良反应报道,以期更好地了解PPAR激动剂毒性作用,为设计出安全性更高的PPAR激动剂提供参考。Peroxisome proliferator-activated receptors(PPAR)are important nuclear receptors that regulate the expression of genes responsible for energy metabolism,inflammatory response,cellular development and differentiation.Their agonists have been developed for the treatment of metabolic diseases such as diabetes,dyslipidemia and atherosclerosis.However,the adverse effects of PPAR agonists limit their use in clinical practice.This paper summarizes the types of toxicity and toxicity mechanisms associated with isotype-specific PPAR agonists and presents reports of adverse reactions to dual PPAR agonists and pan-PPAR agonists in clinical trials in order to better understand the toxic effects of PPAR agonists and provide references for the design of safer PPAR agonists.

关 键 词：过氧化物酶体增殖物激活受体 激动剂 肝毒性 心脏毒性 肌肉毒性 致癌性 

分 类 号：R977[医药卫生—药品] R994.11[医药卫生—药学]