LEI-515

LEI-515 is a peripherally restricted small molecule inhibitor of monoacylglycerol lipase (MAGL). MAGL is the principal enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid. By inhibiting MAGL, LEI-515 increases 2-AG levels and reduces the production of pro-inflammatory arachidonic acid and its downstream eicosanoids. Unlike global MAGL inhibitors, LEI-515 is designed to have limited brain penetration, thereby avoiding central nervous system (CNS)-mediated side effects such as catalepsy or cannabinoid-like behavioral effects. It has been investigated in preclinical models for its potential to attenuate ventilator-induced lung injury (VILI) and acute respiratory distress syndrome (ARDS) by reducing neutrophil activation, pro-inflammatory cytokine levels (e.g., IL-1β, CXCL2), and NF-κB signaling.