Tailoring FXR Modulators for Intestinal Specificity: Recent Progress and Insights

Molecules. 2024 Apr 27;29(9):2022. doi: 10.3390/molecules29092022.

Abstract

While FXR has shown promise in regulating bile acid synthesis and maintaining glucose and lipid homeostasis, undesired side effects have been observed in clinical trials. To address this issue, the development of intestinally restricted FXR modulators has gained attention as a new avenue for drug design with the potential for safer systematic effects. Our review examines all currently known intestinally restricted FXR ligands and provides insights into the steps taken to enhance intestinal selectivity.

Keywords: bile acid synthesis; drug design; farnesoid X receptor (FXR); intestinal selectivity; metabolic diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / chemistry
  • Bile Acids and Salts / metabolism
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Ligands
  • Receptors, Cytoplasmic and Nuclear* / metabolism

Substances

  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Ligands
  • Bile Acids and Salts

Grants and funding

AM would like to thank the Student Research Incentive Fund (SRIF) from the University of Health Sciences and Pharmacy in St. Louis.