1072902-88-5Relevant academic research and scientific papers
Assay and inhibition of diacylglycerol lipase activity
Johnston, Meghan,Bhatt, Shachi R.,Sikka, Surina,Mercier, Richard W.,West, Jay M.,Makriyannis, Alexandros,Gatley, S. John,Duclos Jr., Richard I.
, p. 4585 - 4592 (2012/08/08)
A series of N-formyl-α-amino acid esters of β-lactone derivatives structurally related to tetrahydrolipstatin (THL) and O-3841 were synthesized that inhibit human and murine diacylglycerol lipase (DAGL) activities. New ether lipid reporter compounds were developed for an in vitro assay to efficiently screen inhibitors of 1,2-diacyl-sn-glycerol hydrolysis and related lipase activities using fluorescence resonance energy transfer (FRET). A standardized thin layer chromatography (TLC) radioassay of diacylglycerol lipase activity utilizing the labeled endogenous substrate [1″- 14C]1-stearoyl-2-arachidonoyl-sn-glycerol with phosphorimaging detection was used to quantify inhibition by following formation of the initial product [1″-14C]2-arachidonoylglycerol and further hydrolysis under the assay conditions to [1-14C]arachidonic acid.
Tetrahydrolipstatin analogues as modulators of endocannabinoid 2-arachidonoylglycerol metabolism
Ortar, Giorgio,Bisogno, Tiziana,Ligresti, Alessia,Morera, Enrico,Nalli, Marianna,Di Marzo, Vincenzo
experimental part, p. 6970 - 6979 (2009/11/30)
A series of 21 analogues of tetrahydrolipstatin (THL, 1) were synthesized and tested as inhibitors of the formation or hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Three of the novel compounds, i.e., 11, 13, and 15, inhibited 2-AG formation via the diacylglycerol lipase α (DAGLα) with IC50 values lower than 50 nM (IC50 of THL = 1 μM) and were between 23- and 375-fold selective vs 2-AG hydrolysis by monoacylglycerol lipase (MAGL) as well as vs cannabinoid CB1 and CB2 receptors and anandamide hydrolysis by fatty acid amide hydrolase (FAAH). Three other THL analogues, i.e., 14, 16, and 18, were slightly more potent than THL against DAGLα and appreciably selective vs MAGL, CB receptors, and FAAH (15-26-fold). One compound, i.e., 8, was a potent inhibitor of MAGL-like activity (IC50 = 0.41 μM), and relatively (～7-fold) selective vs the other targets tested.
