Miyachi Hiroyuki
Institute of Molecular and Cellular Biosciences, University of Tokyo, Laboratory of Bioorganic Chemistry, Department of Structural Biology, 1-1-1 Yayoi, Bunkyo-ku, 113-0032, Japan.
IDrugs. 2004 Aug;7(8):746-54.
The understanding of the functions of the nuclear receptor peroxisome proliferator-activated receptor a (PPARalpha) as a regulator of lipid and lipoprotein homeostasis, and the rapid development of parallel high-throughput screening assays to evaluate the activity toward other PPAR subtypes (PPARdelta and PPARgamma), have provided an opportunity to develop novel PPARalpha-selective, PPARalpha/gamma dual and PPAR pan agonists for the treatment of various metabolic diseases. This review focuses on the molecular pharmacology of PPARalpha, and summarizes recent literature and patent applications disclosing medicinal chemistry strategies to identify new PPARalpha-selective agonists. The species selectivity of some classes of PPARalpha-selective agonists in response to in vitro PPARalpha transactivation activity is also reported.
对核受体过氧化物酶体增殖物激活受体α（PPARα）作为脂质和脂蛋白稳态调节剂功能的理解，以及用于评估对其他PPAR亚型（PPARδ和PPARγ）活性的平行高通量筛选测定法的迅速发展，为开发用于治疗各种代谢疾病的新型PPARα选择性、PPARα/γ双重和PPAR泛激动剂提供了机会。本综述聚焦于PPARα的分子药理学，并总结了近期披露用于鉴定新型PPARα选择性激动剂的药物化学策略的文献和专利申请。还报道了某些类别的PPARα选择性激动剂在体外PPARα反式激活活性方面的物种选择性。
