In humans, two forms of diacylglycerol lipase, DAGLα and DAGLβ, generate the endocannabinoid 2-arachidonoyl glycerol (2-AG; ) by attacking DAG at the sn-1 position. LEI-106 is a potent in vitro inhibitor of sn-1 DAGLα (IC50 = 18 nM). It blocks the hydrolysis of sn-1-oleoyl-2-AG, the natural substrate of DAGLα, with a Ki value of 0.7 μM. LEI-106 inhibits the hydrolysis of 2-AG by the monoacylglycerol lipase ABHD6 in mouse brain membrane homogenates and in HEK293T cell membrane preparations (Ki = 0.8 μM).
