Recent progress in research on peroxisome proliferator-activated receptor alpha-selective ligands.
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.
Miyachi
Hiroyuki
H
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. miyachi@iam.u-tokyo.ac.jp
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D020675:Peroxisomes / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D047493:PPAR alpha