关键词： 2-AG, 2-arachidonoyl glycerol 2-Arachidaoylglycerol 2-OG, 2-oleoylglycerol 4-NPA, 4-nitrophenylacetate 7-HCA, 7-hydroxycoumarinyl arachidonate AA, arachidonic acid ABHD6 and ABHD12, α/β-hydrolase 6 and 12 ABP, activity-based probes ABPP, activity-based protein profiling AD, Alzheimer's disease AEA, anandamide Arachidonic acid BCRP, breast cancer resistant protein CB1R and CB2R, cannabinoid receptors CC-ABPP, click chemistry activity-based protein profiling CFA, complete Freund's adjuvant CNS, central nervous system COX, cyclooxygenases CYP, cytochrome P450 proteins Cancer DAG, diacylglycerol DAGLs, diacylglycerol lipases DTT, dithiothreitol Drug discovery EAE, encephalomyelitis EI, enzyme–inhibitor complex FAAH, amide hydrolase FFAs, free fatty acids FP, fluorophosphonate FP-Rh, fluorophosphonate-rhodamine FQ, fit quality HFD, high-fat diet HFIP, hexafluoroisopropyl LC–MS, liquid chromatographic mass spectrometry LFD, low-fat diet MAGL, monoacylglycerol lipase MAGs, monoglycerides MS, multiple sclerosis Metabolic syndrome Monoacylglycerol lipases NAM, N-arachidonoyl maleimide NHS, N-hydroxysuccinimidyl Neuroinflammation OCT2, organic cation transporter 2 P-gp, P-glycoprotein PA, phosphatidic acid PD, Parkinson's disease PET, positron emission tomography PGE2, prostaglandin PGs, prostaglandins PK, pharmacokinetic PLA2G7, phospholipase A2 group VII SAR, structure–activity relationship SBDD, structure-based drug design SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis THL, tetrahydrolipstatin cPLA2, cytosolic phospholipase A2

来  源：   DOI：10.1016/j.apsb.2019.10.006   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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, anti-inflammatory, 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.
摘要：
单酰基甘油脂肪酶（MAGL）是一种丝氨酸水解酶，在催化甘油单酯水解为甘油和脂肪酸中起着至关重要的作用。它通过将丰富的内源性大麻素2-花生四烯酸甘油降解为花生四烯酸，将内源性大麻素和二十烷酸系统连接在一起，前列腺素和其他炎症介质的前体。MAGL抑制剂被认为是许多治疗领域的重要药物。包括抗伤害性,抗焦虑药,抗炎,甚至抗癌。目前,ABX-1431，MAGL的一流抑制剂，正在进入神经系统疾病和其他疾病的临床2期研究。这篇综述总结了MAGL的多种（病理）生理作用，并将对MAGL抑制剂的发展进行概述。尽管已经报道了大量的MAGL抑制剂,仍然需要新的抑制剂，特别是可逆的。
公众号