Disulfiram is an inhibitor of human purified monoacylglycerol lipase, the enzyme regulating 2-arachidonoylglycerol signaling.

Abstract

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.

• Authors: Geoffray Labar, Cédric Bauvois, Giulio G Muccioli, Johan Wouters, Didier M Lambert
• Journal: Chembiochem : a European journal of chemical biology (Chembiochem) Vol. 8 Issue 11 Pg. 1293-7 (Jul 23 2007) ISSN: 1439-4227 [Print] Germany
• PMID: 17579916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arachidonic Acids
• Endocannabinoids
• Glycerides
• glyceryl 2-arachidonate
• Monoacylglycerol Lipases
• Disulfiram

Topics

• Arachidonic Acids (metabolism)
• Disulfiram (pharmacology)
• Endocannabinoids
• Glycerides (metabolism)
• Humans
• Molecular Structure
• Monoacylglycerol Lipases (antagonists & inhibitors, genetics, isolation & purification, metabolism)
• Signal Transduction (drug effects)