molecules of the month

Context. MAGLi 432 (Roche) is a novel, reversible monoacylglycerol lipase (MAGL) inhibitor. There has been increasing interest in the role of inflammation and blood-brain barrier dysfunction in neurology. The appeal of MAGL as an anti-neuroinflammatory therapeutic target comes from its hallmark role as the enzyme that links the endocannabinoid and eicosanoid systems together by modulating the degradation of the most abundant endocannabinoid in the brain, arachidonoylglycerol (2-AG), to arachidonic acid which is a precursor of prostaglandins and other pro-inflammatory molecules. Unsurprisingly, inhibitors targeting MAGL are being evaluated as nociceptive, anxiolytic, anti-inflammatory, and even anti-cancer agents. At least 20 MAGL inhibitors have been reported, the most advanced of which is Lundbeck’s Lu AG06466 (ABX-1431 prior to being acquired) which, despite disappointing…