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]

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