Farnesoid X receptor (FXR): Structures and ligands

Area of Science:

• Hepatology
• Endocrinology
• Pharmacology

Background:

• Farnesoid X receptor (FXR) is a nuclear receptor primarily expressed in the liver and intestine.
• FXR plays a crucial role in regulating bile acid homeostasis, as well as carbohydrate and lipid metabolism.
• Dysregulation of FXR is implicated in various liver diseases, making it a significant therapeutic target.

Purpose of the Study:

• To review the structural characteristics of Farnesoid X receptor (FXR), with a focus on its ligand-binding domain.
• To summarize the development of small molecule modulators (agonists and antagonists) targeting FXR.
• To highlight the therapeutic potential of FXR-targeting agents for bile acid-related liver diseases.

Main Methods:

• Literature review of studies on FXR structure and function.
• Analysis of clinical trial data for FXR-targeting small molecules.
• Summary of reported FXR agonists and antagonists.

Main Results:

• FXR's ligand-binding domain structure is key to its function.
• Several small molecules targeting FXR have been developed, with some in clinical trials.
• Obeticholic acid (OCA) is the first approved FXR-targeting drug.

Conclusions:

• FXR is a validated drug target for liver diseases.
• The development of FXR modulators offers promising therapeutic strategies.
• Further research into FXR structure-activity relationships will advance drug discovery.