Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy,neurological and metabolic disorders

作     者：Hui Deng Weimin Li Hui Deng;Weimin Li

作者机构：Precision Medicine Key Laboratory of Sichuan Province&Precision Medicine CenterWest China HospitalSichuan UniversityChengdu 610041China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2020年第10卷第4期

页      面：582-602页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.21807076) the Sichuan Natural Science Foundation,China(No.2019YJ0112). 

主　　题：Monoacylglycerol lipases 2-Arachidaoylglycerol Arachidonic acid Drug discovery Cancer Neuroinflammation Metabolic syndrome 

摘      要：Monoacylglycerol lipase(MAGL)is a serine hydrolase that plays a crucial role catalysing the hydrolysis of monoglycerides into glycerol and fatty acids.It links the endocannabinoid and eicosanoid systems together by degradation of the abundant endocannabinoid 2-arachidaoylglycerol into arachidonic acid,the precursor of prostaglandins and other inflammatory mediators.MAGL inhibitors have been considered as important agents in many therapeutic fields,including anti-nociceptive,anxiolytic,antiinflammatory,and even anti-cancer.Currently,ABX-1431,a first-in-class inhibitor of MAGL,is entering clinical phase 2 studies for neurological disorders and other diseases.This review summarizes the diverse(patho)physiological roles of MAGL and will provide an overview on the development of MAGL inhibitors.Although a large number of MAGL inhibitors have been reported,novel inhibitors are still required,particularly reversible ones.