Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance
Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance
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微粒体前列腺素E2合酶1及其抑制剂分子机制及治疗意义
DOI：
10.1016/j.phrs.2021.105977
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发表时间：
2021-11-24
影响因子：
9.3
通讯作者：
Zhou，Hua
中科院分区：
文献类型：
--
作者：
Zhang，Yan-Yu;Yao，Yun-Da;Zhou，Hua
炎症与环氧合酶-2/微粒体前列腺素E2合成酶-1/前列腺素E2(COX-2/mPGES-1/PGE2)磷脂代谢链异常密切相关。在临床实践中，非甾体抗炎药(NSAIDs)作为COX-2酶活性的上游抑制剂被广泛应用于阻断COX-2级联反应以减轻炎症反应。然而，非类固醇抗炎药也会因为抑制其他前列腺素的生成而引起心血管和胃肠道副作用。为了避免这一点，靶向下游的mPGES-1而不是上游的COX更好地选择性地阻断炎症性疾病中过表达的PGE2。一些候选的mPGES-1抑制剂，包括合成化合物、天然产物和现有的抗炎药物，在体外实验中被证明是有效的。经过20年对mPGES-1及其抑制剂的深入研究，ISC 27864已完成II期临床试验。在这篇综述中，我们打算总结mPGES-1抑制剂，重点是它们的抑制特异性，并对未来的药物开发进行展望。
Inflammation is closely linked to the abnormal phospholipid metabolism chain of cyclooxygenase-2/microsomal prostaglandin E2synthase-1/prostaglandin E2(COX-2/mPGES-1/PGE2). In clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) as upstream COX-2 enzyme activity inhibitors are widely used to block COX-2 cascade to relieve inflammatory response. However, NSAIDs could also cause cardiovascular and gastrointestinal side effects due to its inhibition on other prostaglandins generation. To avoid this, targeting downstream mPGES-1 instead of upstream COX is preferable to selectively block overexpressed PGE2in inflammatory diseases. Some mPGES-1 inhibitor candidates including synthetic compounds, natural products and existing anti-inflammatory drugs have been proved to be effective in in vitro experiments. After 20 years of in-depth research on mPGES-1 and its inhibitors, ISC 27864 have completed phase II clinical trial. In this review, we intend to summarize mPGES-1 inhibitors focused on their inhibitory specificity with perspectives for future drug development.