Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University.
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(9):703-723. doi: 10.2183/pjab.93.044.
Non-steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory and anti-tumor effects by reducing prostaglandin (PG) production via the inhibition of cyclooxygenase (COX). However, the gastrointestinal, renal and cardiovascular side effects associated with the pharmacological inhibition of the COX enzymes have focused renewed attention onto other potential targets for NSAIDs. PGH, a COX metabolite, is converted to each PG species by species-specific PG terminal synthases. Because of their potential for more selective modulation of PG production, PG terminal synthases are now being investigated as a novel target for NSAIDs. In this review, I summarize the current understanding of PG terminal synthases, with a focus on microsomal PGE synthase-1 (mPGES-1) and PGI synthase (PGIS). mPGES-1 and PGIS cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis. mPGES-1 and PGIS are expected to be attractive alternatives to COX as therapeutic targets for several diseases, including inflammatory diseases and cancer.
非甾体抗炎药（NSAIDs）通过抑制环氧化酶（COX）来减少前列腺素（PG）的产生，从而发挥其抗炎和抗肿瘤作用。然而，与 COX 酶的药理学抑制相关的胃肠道、肾脏和心血管副作用，使人们重新关注 NSAIDs 的其他潜在靶点。PGH 是 COX 的代谢产物，被特异性 PG 末端合成酶转化为每种 PG 物质。由于它们在 PG 产生的更选择性调节方面的潜力，PG 末端合成酶现在作为 NSAIDs 的新靶点正在被研究。在这篇综述中，我总结了对 PG 末端合成酶的当前理解，重点是微粒体 PGE 合酶-1（mPGES-1）和 PGI 合酶（PGIS）。mPGES-1 和 PGIS 协同加剧炎症反应，但对肿瘤发生有相反的影响。mPGES-1 和 PGIS 有望成为 COX 的有吸引力的替代治疗靶点，用于多种疾病，包括炎症性疾病和癌症。
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