LEI-106

LEI-106 (CAS No.: 1620582-23-1) is a potent dual inhibitor of diacylglycerol lipase alpha (DAGL-α) and α/β-hydrolase domain-containing protein 6 (ABHD6), key enzymes involved in the biosynthesis and metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG). As a small-molecule modulator of lipid signaling pathways, LEI-106 effectively suppresses DAGL-α activity at nanomolar potency in cellular systems and exhibits micromolar inhibitory activity against ABHD6, thereby coordinately regulating both the production and degradation of 2-AG. Mechanistically, it blocks DAGL-α-mediated hydrolysis of endogenous diacylglycerol substrates and reduces endothelial-derived 2-AG levels without significantly altering broader cannabinoid or diacylglycerol pools, indicating a degree of pathway selectivity. In biochemical and cellular assays, LEI-106 demonstrates robust inhibition of DAGL-α-dependent lipid hydrolysis and ABHD6-mediated 2-AG turnover, supporting its utility as a chemical probe for dissecting endocannabinoid signaling networks. This compound is widely applied in studies of metabolic regulation, neurobiology, and inflammation, including models of diet-induced obesity and metabolic syndrome, where modulation of lipid mediators is of interest. Experimental concentrations and dosing regimens vary depending on assay format, cell type, and in vivo study design, but its activity profile makes it particularly suitable for mechanistic studies and early-stage drug discovery targeting lipid metabolic enzymes.