Document Report Card

ID: ALA1148757

Journal: J Med Chem

Title: Nongenomic actions of bile acids. Synthesis and preliminary characterization of 23- and 6,23-alkyl-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5.

Authors: Pellicciari R, Sato H, Gioiello A, Costantino G, Macchiarulo A, Sadeghpour BM, Giorgi G, Schoonjans K, Auwerx J.

Abstract: 23-Alkyl-substituted and 6,23-alkyl-disubstituted derivatives of chenodeoxycholic acid are identified as potent and selective agonists of TGR5, a G-protein coupled receptor for bile acids (BAs). In particular, we show that methylation at the C-23(S) position of natural BAs confers a marked selectivity for TGR5 over FXR, while the 6alpha-alkyl substitution increases the potency at both receptors. The present results allow for the first time a pharmacological differentiation of genomic versus nongenomic effects mediated by BA derivatives.

CiteXplore: 17685603

DOI: 10.1021/jm070633p