KT172 is a non-selective inhibitor of diacylglycerol lipase α (DAGLα) and DAGLβ.1 It inhibits DAGL-mediated hydrolysis of 1-stearoyl-2-arachidonoylglycerol in HEK293T cell membranes expressing recombinant DAGLα or DAGLβ (IC50s = 140 and 60 nM, respectively). KT172 also inhibits α/β-hydrolase 6 (ABHD6; IC50 = 5 nM) and weakly inhibits monoacylglycerol lipase (MAGL; IC50 = 5,000 nM) in a panel of 47 mouse serine hydrolases. It restores nicotine-stimulated GABA release in isolated ventral tegmental area (VTA) dopamine neurons from rats chronically exposed to nicotine when used at a concentration of 1 μM.2 KT172 decreases production of 2-arachidonoyl glycerol and subsequently reduces arachidonic acid , prostaglandin E2 , and PGD2 in thioglycolate-stimulated peritoneal macrophages when administered at a dose of 5 mg/kg in mice.1
References
1. Hsu, K.L., Tsuboi, K., Adibekian, A., et al. DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nature Chemical Biology 8(12), 999-1007 (2012).
2. Buczynski, M.W., Herman, M.A., Hsu, K.L., et al. Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure. Proc. Natl. Acad. Sci. U.S.A. 113(4), 1086-1091 (2016).