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] Related Links Therapeutic potential of endocannabinoid-hydrolysing enzyme inhibitors. [Basic Clin Pharmacol Toxicol. 2007] PMID:17910610 Brain monoglyceride lipase participating in endocannabinoid inactivation. [Proc Natl Acad Sci U S A. 2002] PMID:12136125 RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol. [Mol Pharmacol. 2004] PMID:15272052 URB602 inhibits monoacylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. [Chem Biol. 2007] PMID:18096504 A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. [Chem Phys Lipids. 2002] PMID:12505697