Phospholipase A2 inhibitors as potential therapeutic agents for the treatment of inflammatory diseases.

IMPORTANCE OF THE FIELD: The various phospholipase A(2) (PLA(2)) types have been implicated in diverse kinds of lipid signaling and inflammatory diseases. Rheumatoid arthritis, lung inflammation, neurological disorders, such as multiple sclerosis, cardiovascular diseases, including atherosclerosis, and cancer are included among the diseases where PLA(2) enzymes are involved. Thus, there is a great interest in developing potent and selective PLA(2) inhibitors and some of them have entered clinical trials. AREAS COVERED IN THIS REVIEW: This review article discusses the role of each PLA(2) class in inflammatory diseases and the advances in the development of inhibitors presented in patent literature from January 2004 to May 2009. WHAT THE READER WILL GAIN: PLA(2)s cluster in four main types: secreted sPLA(2), cytosolic cPLA(2), Ca(2+)-independent iPLA(2) and lipoprotein-associated LpPLA(2). Each of those types has been implicated in diverse kinds of inflammatory diseases. Readers will rapidly gain an overview of the various PLA(2) inhibitors reported in the patent literature in the past 5 years. Furthermore, the readers will learn the difficulties related to the development of PLA(2) inhibitors as new drugs and also the different companies and research groups that are the main players in the field. TAKE HOME MESSAGE: Although the role of each PLA(2) is not yet distinct in different diseases, the development and future use of different PLA(2) inhibitors to treat human disease seems very promising.