Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review

被引：35

作者：

Psarra, Anastasia ^{[1
]}

Nikolaou, Aikaterini ^{[1
]}

Kokotou, Maroula G. ^{[1
]}

Limnios, Dimitris ^{[1
]}

Kokotos, George ^{[1
]}

机构：

[1] Univ Athens, Dept Chem, Athens, Greece

来源：

EXPERT OPINION ON THERAPEUTIC PATENTS | 2017年 / 27卷 / 09期

关键词：

Cancer; inflammation; inhibitors; microsomal prostaglandin E-2 synthase-1; prostaglandin E-2; ANTIINFLAMMATORY DRUGS NSAIDS; MPGES-1; INHIBITOR; PROINFLAMMATORY CYTOKINES; THERAPEUTIC TARGET; PHOSPHOLIPASE A(2); INDUCED ARTHRITIS; INDUCIBLE ENZYME; SCREENING ASSAY; INDUCED PYRESIS; MURINE MPGES-1;

D O I：

10.1080/13543776.2017.1344218

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Introduction: Microsomal prostaglandin E-2 synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E-2 (PGE(2)) generation. It is strongly upregulated in inflamed tissues and overexpressed in tumors and it has been recognized as a key enzyme in inflammatory diseases such as arthritis, atherosclerosis, stroke and cancer. Thus, a great effort has been devoted in developing synthetic mPGES-1 inhibitors as novel anti-inflammatory agents. Areas covered: This review article summarizes the mPGES-1 inhibitors presented in patent literature from 2000 to August 2016 and their biological evaluation, discussing their activities in vitro and in vivo. Expert opinion: The side effects of NSAIDs and COX-2 inhibitors on the gastrointestinal tract and the cardiovascular system showcase the urgent need for the discovery of novel potent and safe anti-inflammatory drugs. mPGES-1 inhibitors may present superior safety in comparison to existing anti-inflammatory drugs. The first synthetic inhibitor of mPGES-1 was reported in 2001 and up to now a variety of structurally different inhibitors has been developed. However, only recently two inhibitors entered clinical trials and none has reached yet the market. More preclinical and clinical studies on mPGES-1 inhibitors are needed to realize if indeed they may become novel agents for the treatment of inflammation and cancer.

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页码：1047 / 1059

页数：13

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