Pharmacodynamics recent advances of a lipoprotein-associated phospholipase A2 specific inhibitor darapladib / 中国药学杂志

ABSTRACT

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of phospholipases superfamily which can hydrolyze oxidative phospholipid in low density lipoprotein (LDL), and produce two proinflammatory mediators including lysophosphatidylcholine (IvsoPC) and oxidized free fatty acid. Thus, Lp-PLA2 is believed to mediate the inflammatory processes that lead to atherogenesis. Recent studies indicated that Lp-PLA2 acts as a new marker in the inflammatory process and is an independent predictor of the cardiovascular diseases. Many Lp-PLA2-targeted inhibitors have been designed to deal with the key enzyme involving in atherosclerosis. Darapladib is the specific inhibitor which is closest to the market among the rest and is drawn wide attention as an emerging therapy for atherosclerosis, and the clinical phase III trials have been completed. Numerous experiments have confirmed that Darapladib could decrease the activity of Lp-PLA2, reduce inflammatory reaction and disrupt the development of atherosclerosis. In this paper, the authors summarized the mechanism of Lp-PLA2 and Darapladib in atherosclerosis, and the recent advances on the pharmacodynamics of Darapladib in recent years.