1. Academic Validation
  2. 5beta-Cholane activators of the farnesol X receptor

5beta-Cholane activators of the farnesol X receptor

  • J Steroid Biochem Mol Biol. 2005 Mar;94(4):311-8. doi: 10.1016/j.jsbmb.2004.11.012.
Junichi Fukuchi 1 Ching Song Qing Dai Richard A Hiipakka Shutsung Liao
Affiliations

Affiliation

  • 1 Ben May Institute for Cancer Research, Department of Biochemistry and Molecular Biology, The University of Chicago, IL 60637, USA.
Abstract

The farnesoid X receptor (FXR) is activated by bile acids, natural agonists for this nuclear receptor. FXR-target genes play important roles in Cholesterol and lipid metabolism. We have found that a series of 5beta-cholanic acid derivatives, even though without a hydroxyl group or any Other substituent on the steroidal rings, can activate FXR more potently than hydroxylated bile acids in a reporter gene assay. The most potent compound among these derivatives, N-methyl-5beta-glycocholanic acid (NMGCA), induces the formation of receptor/coactivator complex in a gel-shift assay and also increases the expression of FXR target genes in human hepatoma HepG2 cells. Furthermore, in rats, NMGCA causes hypolipidemic effects as well as induction of the FXR target genes in liver. Our results suggest that NMGCA and its derivatives are important FXR activators in the study of the physiological functions of FXR and are potentially useful as pharmaceutical agents for treatment of Cholesterol and lipid-related diseases.

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