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ID: ALA1151781
Journal: Bioorg Med Chem Lett
Title: Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling.
Authors: Hoover HS, Blankman JL, Niessen S, Cravatt BF.
Abstract: The endocannabinoid 2-arachidonoylglycerol (2-AG) has been implicated as a key retrograde mediator in the nervous system based on pharmacological studies using inhibitors of the 2-AG biosynthetic enzymes diacyglycerol lipase alpha and beta (DAGL-alpha/beta). Here, we show by competitive activity-based protein profiling that the DAGL-alpha/beta inhibitors, tetrahydrolipstatin (THL) and RHC80267, block several brain serine hydrolases with potencies equal to or greater than their inhibitory activity against DAGL enzymes. Interestingly, a minimal overlap in target profiles was observed for THL and RHC80267, suggesting that pharmacological effects observed with both agents may be viewed as good initial evidence for DAGL-dependent events.
CiteXplore: 18657971