Darapladib binds to lipoprotein-associated phospholipase A2 with meaningful interactions

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-PLA2 inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-PLA2 through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-PLA2. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.