Med Res Rev. 2014 Jul;34(4):825-55. doi: 10.1002/med.21306.
Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid (AA) into PGH2 that is further metabolized by terminal prostaglandin (PG) synthases into biologically active PGs, for example, prostaglandin E2 (PGE2), prostacyclin I2 (PGI2), thromboxane A2 (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 alpha (PGF2α). Among them, PGE2 is a widely distributed PG in the human body, and an important mediator of inflammatory processes. The successful modulation of this PG provides a beneficial strategy for the potential anti-inflammatory therapy. For instance, nonsteroidal anti-inflammatory agents (NSAIDs), both classical nonselective (cNSAIDs) and the selective COX-2 inhibitors (coxibs) attenuate the generation of PGH2 from AA that in turn reduces the synthesis of PGE2 and modifies the inflammatory conditions. However, the long-term use of these agents causes severe side effects due to the nonselective inhibition of other PGs, such as PGI2 and TXA2, etc. Microsomal prostaglandin E2 synthase-1 (mPGES-1), a downstream PG synthase, specifically catalyzes the biosynthesis of COX-2-derived PGE2 from PGH2, and describes itself as a valuable therapeutic target for the treatment of acute and chronic inflammatory disease conditions. Therefore, the small molecule inhibitors of mPGES-1 would serve as a beneficial anti-inflammatory therapy, with reduced side effects that are usually associated with the nonselective inhibition of PG biosynthesis.
环氧化酶（COX-1 和 COX-2）催化花生四烯酸（AA）转化为 PGH2，PG 末端合成酶进一步将其代谢为生物活性 PG，例如前列腺素 E2（PGE2）、前列环素 I2（PGI2）、血栓素 A2（TXA2）、前列腺素 D2（PGD2）和前列腺素 F2 alpha（PGF2α）。其中，PGE2 是人体内广泛分布的 PG，也是炎症过程的重要介质。成功调节这种 PG 为潜在的抗炎治疗提供了有益的策略。例如，非甾体抗炎药（NSAIDs），包括经典的非选择性（cNSAIDs）和选择性 COX-2 抑制剂（coxibs），可减弱 AA 生成 PGH2，从而减少 PGE2 的合成并改变炎症状态。然而，由于对其他 PG（如 PGI2 和 TXA2 等）的非选择性抑制，这些药物的长期使用会导致严重的副作用。微粒体前列腺素 E2 合酶-1（mPGES-1）是一种下游 PG 合酶，特异性催化 COX-2 衍生的 PGE2 从 PGH2 的生物合成，是治疗急性和慢性炎症性疾病的有价值的治疗靶点。因此，mPGES-1 的小分子抑制剂将作为一种有益的抗炎治疗方法，减少通常与 PG 生物合成的非选择性抑制相关的副作用。
