Related Experiment Videos
Effects of chemical modification of ursodeoxycholic acid on TGR5 activation
Yusuke Iguchi1, Tomoko Nishimaki-Mogami, Masafumi Yamaguchi
1Faculty of Pharmaceutical Science, Hiroshima International University, Kure, Hiroshima 737–0112, Japan. y-iguchi@ps.hirokoku-u.ac.jp
Abstract:
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.
Related Concept Videos
Drugs for Treatment of Ulcerative Colitis in IBD
Drug Metabolism: Phase II Reactions
Phase II Reactions: Glucuronidation
GPCRs Regulate Adenylyl Cylase Activity
Two...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase