The regulation of the catalytic activity of the various phospholipase A2 enzymes is of high importance because these enzymes are involved in various pathological conditions such as arthritis, cardiovascular diseases, neurological diseases, and cancer. Thus, a great effort has been devoted in developing synthetic inhibitors as new agents to treat inflammatory diseases. Some of them have reached clinical trials. Areas covered: This review article discusses the phospholipase A2 inhibitors presented in patent literature from October 2012 to June 2016, their activities in vitro and in vivo as well as the results of clinical trials using synthetic PLA2 inhibitors. Expert opinion: None of the inhibitors studied in clinical trials have reached the market yet. The failure of lipoprotein-associated PLA2 inhibitor darapladib to reduce the risk of major coronary events suggests that this enzyme may be a biomarker of vascular inflammation rather than a causal pathway of cardiovascular diseases. These findings, together with the failure of secreted PLA2 inhibitor varespladib for the treatment of cardiovascular disease, indicate that deeper knowledge on these enzymes is needed. Inhibitors of cytosolic PLA2 are in clinical trials against psoriasis and atopic dermatitis.
Keywords: Arthritis; atherosclerosis; autoimmune diseases; cancer; inflammation; inhibitors; phospholipase A2.