1: Chembiochem. 2008 Nov 3;9(16):2704-10.

CAY10499, a novel monoglyceride lipase inhibitor evidenced by an expeditious MGL 
assay.

Muccioli GG, Labar G, 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. giulio.muccioli@uclouvain.be

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.


PMID: 18855964 [PubMed - indexed for MEDLINE]

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