Advances in Small Molecule Research Targeting Monoacylglycerol Lipase in Drug Discovery

Monoacylglycerol lipase (MAGL), a member of the endocannabinoid system (ECS), plays a crucial role in physiological processes such as regulating the signal transduction of the ECS and the eicosanoid system. In recent years, MAGL has been validated as a potential therapeutic target for several human diseases. Small-molecule MAGL inhibitors have shown considerable promise for the treatment of neurodegenerative diseases, depression, and cancer, with several candidates having advanced to clinical trials. This review briefly outlines the structural features and physiological functions of MAGL, highlights the associations between MAGL and human diseases, and systematically discusses small-molecule MAGL inhibitors developed for different disorders, with the goal of providing a reference for the discovery of more potent MAGL inhibitors.