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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Identification of gene-selective modulators of the bile acid receptor FXR.

BAR is a nuclear bile acid receptor (BAR) (FXR) receptor that regulates gene networks involved in cholesterol and bile acid homeostasis. We have identified two classes of synthetic compounds that differentially modulate BAR activity. The first class activates BAR target genes in the predicted fashion and is 25-fold more potent than endogenous bile acids. The second class, represented by AGN34, antagonizes BAR in transient reporter assays. Surprisingly, this compound acts in a gene-selective manner in vivo: it is an agonist on CYP7A1, an antagonist on IBABP, and is neutral on SHP. These findings indicate that synthetic BAR modulators can be developed to regulate transcription in a gene-specific fashion. Given the ability of BAR to regulate several lipid homeostatic pathways, the identification of gene-selective BAR modulators have important implications for the development of improved cholesterol lowering agents.[1]


  1. Identification of gene-selective modulators of the bile acid receptor FXR. Dussault, I., Beard, R., Lin, M., Hollister, K., Chen, J., Xiao, J.H., Chandraratna, R., Forman, B.M. J. Biol. Chem. (2003) [Pubmed]
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