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.

Nongenomic Actions of Bile Acids. Synthesis and Preliminary Characterization of 23-and 6,23-Alkyl-Sobstituted Bile Acid Derivatives as Selective Modulators for the G-Protein Coupled Receptor TGR5

PELLICCIARI, Roberto;GIOIELLO, ANTIMO;MACCHIARULO, Antonio;
2007

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.
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/151504
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