PPARγ ligands and their therapeutic applications: a patent review (2008-2014)
PPARγ ligands and their therapeutic applications: a patent review (2008-2014)
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DOI：
10.1517/13543776.2014.985206
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发表时间：
2015-02-01
影响因子：
6.6
通讯作者：
Makishima, Makoto
中科院分区：
文献类型：
--
作者：
Takada, Ichiro;Makishima, Makoto
PPARgamma调节葡萄糖和脂质代谢、免疫以及细胞生长和分化。噻唑烷二酮（TZD）是用于治疗2型糖尿病的合成的PPAR γ配体。然而，TZDs会引起不良反应，如增加心力衰竭、骨折和膀胱癌的风险。过氧化物酶体增殖物激活受体γ有一个大的配体结合口袋，这使得有可能开发各种过氧化物酶体增殖物激活受体γ配体，导致其治疗应用的专利。涵盖领域：我们总结了最近的专利活动，关于过氧化物酶体增殖物激活受体γ配体和它们的治疗应用从2008年。本文还综述了通过结合PPAR γ配体和其他药物来增加PPAR γ表达和减少PPAR γ副作用的药理学方法。除了表现出选择性治疗活性而没有副作用如骨丢失、体液潴留或体重增加的新型PPAR γ配体之外，已经要求保护用于组合PPAR γ配体和其它化合物的方法以减少副作用和/或增强靶向作用。联合治疗是有用的，但有潜在的意外不良反应的风险。已经提交了用于将PPAR γ配体的临床应用扩展到非代谢性疾病（例如神经和炎症性疾病）和皮肤美白的专利申请，并且需要未来的研究来阐明潜在的机制。
Introduction: PPAR gamma regulates glucose and lipid metabolism, immunity, and cellular growth and differentiation. Thiazolidinediones (TZDs) are synthetic PPAR gamma ligands that are used in the treatment of type 2 diabetes. However, TZDs can cause adverse effects, such as increased risks of heart failure, bone fractures and bladder cancer. PPAR gamma has a large ligand-binding pocket, which makes it possible to develop a variety of PPAR gamma ligands, leading to patents on their therapeutic applications.Areas covered: We summarize recent patent activity regarding PPAR gamma ligands and their therapeutic applications from 2008. Pharmacologic methods to increase PPAR gamma expression and to decrease PPAR gamma adverse effects by combining PPAR gamma ligands with other drugs are also reviewed.Expert opinion: In addition to novel PPAR gamma ligands that exhibit selective therapeutic activity without adverse effects, such as bone loss, fluid retention or weight gain, methods for the combination of PPAR gamma ligands and other compounds have been claimed to decrease adverse effects and/or to enhance targeted effects. Combination therapy is useful but has the potential risk of unexpected adverse effects. Patent applications for expanding clinical application of PPAR gamma ligands to non-metabolic diseases, such as neurological and inflammatory diseases, and to skin whitening have been filed, and future studies are needed to elucidate the underlying mechanisms.