The molecular pharmacological discovery of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) as the master regulator of lipid and lipoprotein homeostasis, and the rapid development of a parallel screening approach to evaluate activity towards other PPAR subtypes (PPARδ, and PPARγ) have provided an opportunity to develop novel PPARα-selective, PPARα/γ dual, and PPAR pan agonists. This review focuses on the molecular pharmacology of PPARα, and summarizes our current design, synthesis, and evaluation of subtype-selective PPARα agonists. The species selectivity of several classes of PPARα selective agonists in response to in vitro PPARα transactivation activity is also reported. These studies should help us to understand the structure-activity relationships and the mode of interaction between ligands and PPARα, and also help to create novel therapeutic choices for the treatment of metabolic disorders.
- Peroxisome proliferator-activated receptor (PPAR)
- Species selectivity
ASJC Scopus subject areas
- Pharmaceutical Science