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.

Article Details

Citation

Copy to clipboard

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

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.

J Med Chem. 2007 Sep 6;50(18):4265-8. Epub 2007 Aug 9.

PubMed ID

17685603 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Chenodeoxycholic acid	Bile acid receptor	EC 50 (nM)	13000	7.2	37	Details