[PPARs as molecular targets for drug discovery].
Peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors. PPARs form the heterodimers with retinoid X receptors (RXRs), and modulate specific gene expressions related to the lipid and carbohydrate metabolism. Since fibrate-type lipid-lowering agents and thiazolidinedione (TZD)-type antidiabetic agents are identified as PPARalpha and gamma agonists, respectively, a number of ligands for PPARs have been developed, including PPAR subtype-selective and dual agonists. Recent report that RXR antagonist exhibited antidiabetic and antiobestic activities in animal model experiments, PPARs partial agonists, antagonists, and RXR antagonists have been also synthesized and their function in vivo are under investigations. In this paper, recent studies on the ligands for the PPAR-RXR heterodimers are reviewed.
Kagechika
Hiroyuki
H
School of Biomedical Science, Tokyo Medical and Dental University.
Miyachi
Hiroyuki
H
D015195:Drug Design; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000502:physiology*; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000502:physiology; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000502:physiology
D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid