选择性PPARγ调节剂的研究新进展

Updated research progress of selective PPARγmodulators

噻唑烷二酮类(thiazolidinediones,TZDs)药物是目前临床使用的唯一的胰岛素增敏剂,用于2型糖尿病的治疗,其疗效确切,但众多的不良反应报道阻碍了该类药物的继续使用。过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)作为TZDs的已知受体,其药效作用和不良反应的相关机制得到深入的研究。为最大程度地保留PPARγ介导的胰岛素增敏药效作用,并尽量减少相关不良反应的发生,"选择性PPARγ调节剂(selective PPARγmodulators,SPPARMs)"的概念被提出和发展,并指导新药研发实践。本文就SPPARMs的定义、化合物分类及作用机制等方面对近年来取得的研究新进展作一综述,并以YR系列化合物的发现为例,展望SPPARMs的潜在应用前景。

Thiazolidinediones(TZDs)are currently the only recognized insulin sensitizers available for the clinical treatment of type 2 diabetes.Although their advantages are recognized,the profiles of numerous adverse effects hinder the continued use of these drugs.Peroxisome proliferator-activated receptorγ(PPARγ)is known as a receptor for TZDs,and its underlying mechanisms of pharmacological actions and adverse effects have been deeply explored.To maximally preserve the PPARγ-mediated insulin sensitizing effects and reduce the occurrence of related adverse effects,the concept of"selective PPARγmodulators(SPPARMs)"has been proposed and developed,guiding the development of new drugs.In this review,we summarize the recent research progress in the definition of SPPARMs,the candidate classification and the molecular underpinnings,as well as present the discovery of the YR series compounds as an example,and discuss the potential application prospects of SPPARMs.