Identification of lead molecules capable of the simultaneous agonism of the PPARƴ and PPARα subtypes for the dual management of diabetes mellitus and dyslipidaemia

Abstract

A poster presentation regarding the identification of lead molecules capable of the simultaneous agonism of the PPARƴ and PPARα subtypes for the dual management of diabetes mellitus and dyslipidaemia. Introduction: This is a rational drug design study aiming to identify lead molecules capable of successfully interacting with more than one Peroxisome Proliferator Activated Receptor (PPAR) subtype in order to simultaneously manage more than one PPAR mediated condition. The PPARs are nuclear receptors involved in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. This study stems from the loss of the glitazone hypoglycaemics (full PPARƴ agonists) from the market due to their unacceptable side effect profile, and from the realisation that full PPARƴ agonism could not be separated from this adverse effect spectrum. It uses the PPARƴ partial agonist angiotensin receptor blocker telmisartan (pdb ID 3VN2) and an experimental fibrate PPARα agonist GW590735 (pdb ID 2P54) to probe these respective PPAR Ligand Binding Pockets (PPAR_LBPs).