1: Chembiochem. 2007 Jul 23;8(11):1293-7. Disulfiram is an inhibitor of human purified monoacylglycerol lipase, the enzyme regulating 2-arachidonoylglycerol signaling. Labar G, Bauvois C, Muccioli GG, Wouters J, Lambert DM. Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculté de Médecine, Université catholique de Louvain, Avenue E. Mounier 73.40 1200 Bruxelles, Belgium. Monoacylglycerol lipase (MAGL) is a key enzyme responsible for the termination of endocannabinoid signaling. Its crucial role in 2-arachidonoylglycerol (2-AG) metabolism, together with the numerous pharmacological properties mediated by this endocannabinoid, emphasize the interest in MAGL as therapeutic target, along with the need to design potent and selective inhibitors. Meanwhile, the complexity of 2-AG degradation pathways underscores the need to use a purified source of enzyme in evaluation studies of new inhibitors. We report here the first heterologous expression and purification of human MAGL. A highly pure protein was obtained and allowed us to measure the affinity of several MAGL inhibitors for the human enzyme. Importantly, disulfiram (tetraethylthiuram disulfide), a compound used to treat alcoholism, and other disulfide-containing compounds were shown to inhibit MAGL with good potency, likely through an interaction with cysteine residues. PMID: 17579916 [PubMed - indexed for MEDLINE] Related Links Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase. [Biochem Biophys Res Commun. 2005] PMID:16181610 Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol. [Br J Pharmacol. 2004] PMID:15492019 RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol. [Mol Pharmacol. 2004] PMID:15272052 Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus. [Nat Neurosci. 2005] PMID:16116451 Development of the first potent and specific inhibitors of endocannabinoid biosynthesis. [Biochim Biophys Acta. 2006] PMID:16466961