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.
Keywords: Atherosclerosis, cancer, FXR antagonists, FXR knockout, glucose homeostasis, guggulsterone, lipid homeostasis,
liver disorders, metabolic disorders, selective bile acid receptor modulators (SBARMs).
Rights & PermissionsPrintExport