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CAY10499, a Novel Monoglyceride Lipase Inhibitor Evidenced by an Expeditious MGL Assay
Author(s) -
Muccioli Giulio G.,
Labar Geoffray,
Lambert Didier M.
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800428
Subject(s) - monoacylglycerol lipase , lipase , monoglyceride , endocannabinoid system , chemistry , enzyme , biochemistry , substrate (aquarium) , glyceride , biology , fatty acid , ecology , receptor
Monoglyceride lipase (MGL) plays a major role in the metabolism of the lipid transmitter 2‐arachidonoylglycerol (2‐AG). This endocannabinoid is known to mediate a large number of physiological processes, and its regulation is thought to be of great therapeutic potential. However, the number of available monoglyceride lipase inhibitors is limited, mostly due to the lack of rapid and accurate pharmacological assays for the enzyme. We have developed a 96‐well‐format assay for MGL using a nonradiolabeled substrate, 4‐nitrophenylacetate. The IC 50 values that were obtained for known inhibitors of MGL using 4‐nitrophenylacetate were similar to those reported by using the radiolabeled form of an endogenous substrate, 2‐oleoylglycerol. In a first small‐scale screening, we identified CAY10499 as a novel monoglyceride lipase inhibitor. Thus, we report here the characterization of this submicromolar inhibitor, which acts on MGL through an unprecedented mechanism for inhibitors of this enzyme.