Potential therapeutic uses of phospholipase A₂inhibitors

The cleavage of the sn-2 ester of membrane phospholipids by phospholipase A2 has long been ascribed as the important initiation step in the production of pro-inflammatory mediators, including prostaglandins, leukotrienes and platelet-activating factor. Consequently, this enzymatic action has been implicated in the pathogenesis of a multitude of diseases, ranging from lung inflammation and arthritis to neural injuries and cardiovascular disease. The three types of phospholipase A2 that have received the most research attention are: secretory phospholipase A2 (sPLA2), cytosolic phospholipase A2 (cPLA2) and lipoprotein-associated phospholipase A2 (LpPLA2). This review will discuss the likely roles of these PLA2 in the development of the disease conditions and recent advances in the development of specific inhibitors, based on the patent literature from December 2000 to December 2003.