Department of Pharmacology, Piramal Life Sciences Limited, 1 Nirlon Complex, Goregaon (E), Mumbai - 400 063, India.
Expert Opin Investig Drugs. 2010 Apr;19(4):489-512. doi: 10.1517/13543781003640169.
PPARgamma full agonists (pioglitazone and rosiglitazone) are the mainstay drugs for the treatment of type 2 diabetes; however, mechanism-based side effects have limited their full therapeutic potential. In recent years, much progress has been achieved in the discovery and development of selective PPARgamma modulators (SPPARgammaMs) as safer alternatives to PPARgamma full agonists.
This review focuses on the preclinical and clinical data of all the SPPARgammaMs discovered so far, retrieved by searching PubMed, Prous Integrity database and company news updates from 1999 to date.
Here we thoroughly discuss SPPARgammaMs' mode of action, briefly examine new ways to identify superior SPPARgammaMs, and finally, compare and contrast the pharmacological and safety profile of various agents.
The preclinical and clinical findings clearly suggest that selective PPARgamma modulators have the potential to become the next generation of PPARgamma agonists: effective insulin sensitizers with a superior safety profile to that of PPARgamma full agonists.
过氧化物酶体增殖物激活受体γ（PPARγ）全激动剂（吡格列酮和罗格列酮）是治疗 2 型糖尿病的主要药物；然而，基于机制的副作用限制了它们的全部治疗潜力。近年来，在发现和开发选择性过氧化物酶体增殖物激活受体γ调节剂（SPPARγMs）作为 PPARγ 全激动剂的更安全替代品方面取得了很大进展。
这篇综述主要关注迄今为止通过搜索 PubMed、Prous 完整性数据库和公司新闻更新从 1999 年到目前为止发现的所有 SPPARγMs 的临床前和临床数据。
在这里，我们深入讨论了 SPPARγMs 的作用模式，简要探讨了识别更优 SPPARγMs 的新方法，最后比较和对比了各种药物的药理学和安全性特征。
临床前和临床研究结果清楚地表明，选择性过氧化物酶体增殖物激活受体γ调节剂有可能成为下一代过氧化物酶体增殖物激活受体γ激动剂：作为有效的胰岛素增敏剂，其安全性优于过氧化物酶体增殖物激活受体γ 全激动剂。
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