Effects of Chemical Modification of Ursodeoxycholic Acid on TGR5 Activation

DOI Web Site Web Site PubMed 2 Citations 28 References Open Access
  • Iguchi Yusuke
    Faculty of Pharmaceutical Science, Hiroshima International University
  • Nishimaki-Mogami Tomoko
    Division of Functional Biochemistry and Genomics, National Institute of Health Sciences
  • Yamaguchi Masafumi
    Faculty of Pharmaceutical Science, Hiroshima International University
  • Teraoka Fumiteru
    Faculty of Pharmaceutical Science, Hiroshima International University
  • Kaneko Tetsuo
    Faculty of Pharmaceutical Science, Hiroshima International University
  • Une Mizuho
    Faculty of Pharmaceutical Science, Hiroshima International University

Search this article

Description

The aim of this study is to examine the ability of the bile acid analogues obtained by chemical modification of ursodeoxycholic acid (UDCA) for TGR5 activation. Eleven UDCA analogues including 3- or 7-methylated UDCAs and amino acid conjugates were investigated as to their ability to activate TGR5 by means of the luciferase assay. It was noteworthy that 7α-methylated UDCA, namely 3α,7β-dihydroxy-7α-methyl-5β-cholanoic acid, had a significantly high affinity for and ability to activate TGR5 as compared to UDCA. Additionally, FXR activation ability of 7α-methylated UDCA was low relative to that of UDCA. However, other modification of UDCA, such as the introduction of methyl group at its C-3 position and oxidation or epimerization of hydroxyl group in the C-3 position, could not elicit such remarkable effect. The present findings would provide a useful strategy for the development of TGR5-selective agonist.

Journal

Citations (2)*help

See more

References(28)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top