Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity

J Med Chem. 2009 Dec 24;52(24):7958-61. doi: 10.1021/jm901390p.


In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C(23)(S)-methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization efforts that have led to the discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and selective TGR5 agonist with remarkable in vivo activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • COS Cells
  • Chlorocebus aethiops
  • Cholic Acids / chemistry
  • Cholic Acids / pharmacokinetics
  • Cholic Acids / pharmacology*
  • Cricetinae
  • Cricetulus
  • Diabetes Mellitus / drug therapy
  • Humans
  • Obesity / drug therapy
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Stereoisomerism


  • 6alpha-ethyl-23(S)-methylcholic acid
  • Cholic Acids
  • GPBAR1 protein, human
  • Receptors, G-Protein-Coupled