Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D.

ABSTRACT: N-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of N-acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and N-acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC₅₀ of 68 μm), but LCA is also a highly potent ligand for TGR5 (EC₅₀ 0.52 μm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC₅₀ of 34 μm). To identify more potent inhibitors of NAPE-PLD, here we used a quench

SUBMITTER: Aggarwal G 

PROVIDER: S-EPMC7247316 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature