[Development of anti-inflammatory drugs targeted against prostaglandin-related molecules]

Prostaglandin E2 (PGE2) is a proinflammatory mediator that is synthesized by cyclooxygenases (COX-1 and COX-2) and prostaglandin E synthases (cPGES-1 and mPGES-1); PGE2 exerts its biological effects by binding to specific receptors. Although non-steroidal anti-inflammatory drugs(NSAIDs), which are non-selective COX inhibitors, have been very often used as painkillers, their side effects such as gastrointestinal hemorrhage remain a serious problem. Therefore, the selective COX-2 inhibitors were developed; the use of these inhibitors exerted anti-inflammatory effects without the increased risk of gastrointestinal events. Unfortunately, however, several clinical studies demonstrated that the inhibition of COX-2 was associated with the increased risk of cardiovascular events. Consequently, mPGES-1 and PGE2 receptors are currently expected to be attractive targets for anti-inflammatory drug development in order to reduce the side effects.