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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Magrioti
Victoria
V
University of Athens, Department of Chemistry, Panepistimiopolis, Athens 15771, Greece.
Kokotos
George
G
D000818:Animals; D002986:Clinical Trials as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D010330:Patents as Topic; D064801:Phospholipase A2 Inhibitors
D004791:Enzyme Inhibitors; D064801:Phospholipase A2 Inhibitors