期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 50, 期 18, 页码 4265-4268出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm070633p
关键词
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23-Alkyl-substituted and 6,23-alkyl-disubstituted derivatives of chenodeoxvcholic 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 6 alpha-alkyl substitution increases the potency at both receptors. The present results allow for the first time a pharmacological differentiation of genomic versus nongenornic effects mediated by BA derivatives.
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