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

Pellicciari, RobertoSato, HiroyukiGioiello, AntimoCostantino, GabrieleMacchiarulo, AntonioSadeghpour, Bahman M.Giorgi, GianlucaSchoonjans, KristinaAuwerx, Johan2009-04-022009-04-02200710.1021/jm070633phttps://infoscience.epfl.ch/handle/20.500.14299/366981768560323-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 derivativesNongenomic 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 TGR5text::journal::journal article::research article