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 6Ralkyl 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-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5 / Pellicciari, R.; Sato, H.; Gioiello, A.; Costantino, Gabriele; Macchiarulo, A.; Sadeghpour, B. M.; Giorgi, G.; Schoonjans, K.; Auwerx, J.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 50:(2007), pp. 4265-4268. [10.1021/jm070633p]
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
COSTANTINO, Gabriele;
2007-01-01
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 6Ralkyl 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 derivativesFile | Dimensione | Formato | |
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