Farnesoid X receptor modulators 2014-present: a patent review

Area of Science:

• Pharmacology
• Hepatology
• Metabolic Diseases

Background:

• The nuclear receptor FXR regulates bile acid, glucose, and lipid homeostasis.
• FXR is a therapeutic target for cholestasis and non-alcoholic fatty liver disease (NAFLD).
• FXR research is highly competitive, with numerous patents and publications.

Purpose of the Study:

• To review recent patent activity (2014-present) for synthetic and natural FXR ligands.
• To analyze the in vitro and in vivo efficacy of these compounds.
• To assess their therapeutic applications and potential in liver diseases.

Main Methods:

• Patent literature review (2014-to date).
• Analysis of synthetic and natural FXR ligands, including bile acid derivatives and non-steroidal compounds.
• Evaluation of reported in vitro and in vivo efficacy data.

Main Results:

• Numerous patents claim steroidal and non-steroidal FXR agonists.
• Approved FXR agonist obeticholic acid has safety concerns, raising questions about class-related issues.
• Efficacy and safety data for many patented compounds remain under investigation.

Conclusions:

• Despite approved therapies, significant safety issues persist for FXR agonists.
• Uncertainty remains regarding the therapeutic potential and safety profile of novel FXR ligands.
• Further development of novel FXR compounds is warranted for cholestasis and NASH.