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

• 来源期刊: 药学学报（英文版）
• 关键词: Monoacylglycerol lipases 2-Arachidaoylglycerol Arachidonic acid Drug discovery Cancer Neuroinflammation Metabolic syndrome
• 年，卷（期）: 2020,（4）
• 页码范围: 582-602
• 页数: 21页
• 语种: 英文

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.