Medicinal chemistry and pharmacological effects of Farnesoid X Receptor (FXR) antagonists

Curr Top Med Chem. 2014;14(19):2188-205. doi: 10.2174/1568026614666141112103516.


The nuclear bile acid sensor farnesoid X receptor (FXR) constitutes a rising target for the treatment of a variety of diseases including metabolic disorders, inflammation and certain forms of cancer. While the research on FXR agonists has yielded many compounds and first clinical candidates, only few FXR antagonists have been discovered so far and the knowledge about their in vivo effects is quite narrow. We have evaluated available in vitro and in vivo studies with FXR antagonists as well as FXR knockout models to elucidate a potential pharmacological use of FXR antagonism. To date, the in vitro and in vivo data suggests that FXR inhibition by knockout or the use of antagonists causes beneficial effects on cholesterol metabolism, ameliorates liver toxicity in cholestasis and can reduce the proliferation and migration of some cancer cell lines. Unfortunately, also many disadvantageous effects are connected with FXR antagonists.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical*
  • Humans
  • Metabolic Diseases / drug therapy*
  • Models, Molecular
  • Pharmaceutical Preparations / metabolism*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*


  • Pharmaceutical Preparations
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor