In vitro activity: ABX-1431 is a highly potent, selective, and orally available, CNS-penetrant MGLL (serine hydrolase monoacylglycerol lipase) inhibitor. Monoacylglycerol lipase (MGLL or MAGL) is a critical point of regulation of both endocannabinoid and eicosanoid signaling pathways in the brain, thereby providing novel therapeutic opportunities for neurological and neurodegenerative diseases. Activity-based protein profiling experiments verify the exquisite selectivity of ABX-1431 for MGLL versus other members of the serine hydrolase class. In vivo, ABX-1431 inhibits MGLL activity in rodent brain (ED50 = 0.5–1.4 mg/kg), increases brain 2-AG concentrations, and suppresses pain behavior in the rat formalin pain model. ABX-1431 is currently under evaluation in human clinical trials.

Kinase Assay: ABX-1431 is a highly potent, selective, and orally available, CNS-penetrant MGLL (serine hydrolase monoacylglycerol lipase) inhibitor. Monoacylglycerol lipase (MGLL or MAGL) is a critical point of regulation of both endocannabinoid and eicosanoid signaling pathways in the brain, thereby providing novel therapeutic opportunities for neurological and neurodegenerative diseases. Activity-based protein profiling experiments verify the exquisite selectivity of ABX-1431 for MGLL versus other members of the serine hydrolase class.

Cell Assay: