Microsomal prostaglandin E2 synthase: a safer target than cyclooxygenases?
Non-steroidal anti-inflammatory drugs (NSAIDs) are inhibitors of the cyclo-oxygenase (COX)-1 and -2 activities of prostaglandin G/H synthase-1 and -2, respectively. They have been extensively used in the treatment of prostaglandin E(2)-mediated chronic inflammatory diseases. Selective COX-2 inhibitors (coxibs), which were developed to provide an alternative with reduced gastrointestinal risk for the traditional NSAIDs, have been associated with an increased incidence of major adverse cardiovascular events. Could the targeting of microsomal prostaglandin E(2) synthase (mPGES-1) lead to novel anti-inflammatory drugs with possibly reduced risks of gastrointestinal and cardiovascular side effects?
Timmers
Leo
L
Laboratory of Experimental Cardiology, University Medical Center Utrecht, the Netherlands. l.timmers@umcutrecht.nl
Pasterkamp
Gerard
G
de Kleijn
Dominique P V
DP
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism