School of Pharmacy, Nanchang University, Nanchang 330006, China.
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Bioorg Med Chem Lett. 2021 Jun 1;41:127986. doi: 10.1016/j.bmcl.2021.127986. Epub 2021 Mar 22.
Monoacylglycerol lipase (MAGL) is the major enzyme that catalyzes the hydrolysis of monoacylglycerols (MAGs). MAGL is responsible for degrading 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain and specific tissues. The inhibition of MAGL could attenuate the inflammatory response. Here, we report a series of reversible non-covalent MAGL inhibitors via virtual screening combined with biochemical analysis. The hit, DC630-8 showed low-micromolar activity against MAGL in vitro, and exhibited significant anti-inflammatory effects.
单酰基甘油脂肪酶（MAGL）是催化单酰基甘油（MAG）水解的主要酶。MAGL 负责在大脑和特定组织中降解 2-花生四烯酸甘油（2-AG）为花生四烯酸（AA）和甘油。MAGL 的抑制作用可以减轻炎症反应。在这里，我们通过虚拟筛选结合生化分析报告了一系列可还原的非共价 MAGL 抑制剂。命中化合物 DC630-8 在体外对 MAGL 具有低微摩尔活性，并表现出显著的抗炎作用。
