Related Experiment Video
Updated: Jun 26, 2025
Author Spotlight: Generation and Manipulation of Rat Intestinal Organoids
Published on: June 23, 2023
Tailoring FXR Modulators for Intestinal Specificity: Recent Progress and Insights
Amanda Morrison1, Bahaa Elgendy1,2
1Center for Clinical Pharmacology, Washington University School of Medicine and University of Health Sciences and Pharmacy, St. Louis, MO 63110, USA.
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.
Insights
New drugs targeting the Farnesyl X Receptor (FXR) are being designed for restricted intestinal action. This approach aims to improve safety by minimizing systemic side effects while maintaining therapeutic benefits.
Area of Science:
- Pharmacology
- Hepatology
- Drug Discovery
Background:
- Farnesyl X Receptor (FXR) plays a key role in bile acid synthesis and glucose/lipid metabolism.
- Clinical trials of systemic FXR modulators have revealed undesirable side effects.
- Intestinal restriction offers a strategy to mitigate systemic toxicity of FXR modulators.
Purpose of the Study:
- To review existing intestinally restricted FXR ligands.
- To analyze strategies for enhancing intestinal selectivity of FXR modulators.
- To provide insights into the development of safer FXR-targeted therapeutics.
Main Methods:
- Comprehensive literature search for intestinally restricted FXR ligands.
- Analysis of chemical and pharmacological properties of identified ligands.
- Evaluation of design strategies for achieving intestinal selectivity.
Main Results:
- Identification of various chemical classes of intestinally restricted FXR ligands.
- Characterization of key structural and physicochemical features contributing to intestinal restriction.
- Summary of approaches used to optimize FXR modulators for targeted intestinal action.
Conclusions:
- Intestinally restricted FXR modulators represent a promising therapeutic strategy.
- Targeted drug design can enhance intestinal selectivity and improve safety profiles.
- Further development in this area holds potential for treating metabolic and liver diseases.
More Related Videos
07:05Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
Published on: December 15, 2017
07:04Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
Published on: February 11, 2017
