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 (PGF_2α). 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.

中文翻译：

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微粒体前列腺素E2合酶1酶的抑制剂可作为新兴的抗炎药物。

环氧合酶（COX-1和COX-2）催化花生四烯酸（AA）转化为PGH ₂，再由末端前列腺素（PG）合成酶进一步代谢成具有生物活性的PG，例如前列腺素E ₂（PGE ₂），前列腺素I ₂（PGI ₂），血栓烷A ₂（TXA ₂），前列腺素D ₂（PGD ₂）和前列腺素F ₂ alpha（_PGF2α）。其中，PGE ₂PG是人体中分布广泛的PG，是炎症过程的重要介质。这种PG的成功调节为潜在的抗炎治疗提供了有益的策略。例如，非甾体类抗炎药（NSAIDs），经典的非选择性（c NSAIDs）和选择性COX-2抑制剂（coxibs）都会削弱AA产生PGH _2的能力，进而降低PGE ₂的合成并改变炎症条件。但是，由于对其他PG（例如PGI ₂和TXA ₂等）的非选择性抑制，长期使用这些药物会导致严重的副作用。微粒前列腺素E ₂下游PG合酶synthase-1（mPGES-1）特异性催化PGH ₂从COX-2衍生的PGE ₂的生物合成，并将其描述为治疗急性和慢性炎症疾病的重要治疗靶标。因此，mPGES-1的小分子抑制剂可作为一种有益的抗炎治疗药物，其副作用通常与非选择性抑制PG生物合成有关，因此可减少副作用。