euphol and celastrol

euphol has been researched along with celastrol* in 1 studies

Other Studies

1 other study(ies) available for euphol and celastrol

Article	Year
Discovery of potent and reversible monoacylglycerol lipase inhibitors. Chemistry & biology, 2009, Oct-30, Volume: 16, Issue:10 Monoacylglycerol lipase (MGL) is a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Previous efforts to design MGL inhibitors have focused on chemical scaffolds that irreversibly block the activity of this enzyme. Here, we describe two naturally occurring terpenoids, pristimerin and euphol, which inhibit MGL activity with high potency (median effective concentration, IC(50) = 93 nM and 315 nM, respectively) through a reversible mechanism. Mutational and modeling studies suggest that the two agents occupy a common hydrophobic pocket located within the putative lid domain of MGL, and each reversibly interacts with one of two adjacent cysteine residues (Cys(201) and Cys(208)) flanking such pocket. This previously unrecognized regulatory region might offer a molecular target for potent and reversible inhibitors of MGL. Topics: Animals; Arachidonic Acids; Binding Sites; Cells, Cultured; Drug Design; Enzyme Inhibitors; Glycerol; HeLa Cells; Humans; Lanosterol; Molecular Dynamics Simulation; Monoacylglycerol Lipases; Neurons; Pentacyclic Triterpenes; Protein Structure, Tertiary; Rats; Rats, Wistar; Triterpenes	2009

Article

Year

Discovery of potent and reversible monoacylglycerol lipase inhibitors.

Chemistry & biology, 2009, Oct-30, Volume: 16, Issue:10

Monoacylglycerol lipase (MGL) is a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Previous efforts to design MGL inhibitors have focused on chemical scaffolds that irreversibly block the activity of this enzyme. Here, we describe two naturally occurring terpenoids, pristimerin and euphol, which inhibit MGL activity with high potency (median effective concentration, IC(50) = 93 nM and 315 nM, respectively) through a reversible mechanism. Mutational and modeling studies suggest that the two agents occupy a common hydrophobic pocket located within the putative lid domain of MGL, and each reversibly interacts with one of two adjacent cysteine residues (Cys(201) and Cys(208)) flanking such pocket. This previously unrecognized regulatory region might offer a molecular target for potent and reversible inhibitors of MGL.

Topics: Animals; Arachidonic Acids; Binding Sites; Cells, Cultured; Drug Design; Enzyme Inhibitors; Glycerol; HeLa Cells; Humans; Lanosterol; Molecular Dynamics Simulation; Monoacylglycerol Lipases; Neurons; Pentacyclic Triterpenes; Protein Structure, Tertiary; Rats; Rats, Wistar; Triterpenes

2009