Drug development strategy based on the nuclear receptor farnesoid X receptor and its application in the treatment of digestive diseases

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is highly expressed mainly in the liver and intestine. As a transcription factor regulating the expression of multiple target genes, FXR not only regulates bile acid, glycolipid, and microbial metabolism through a number of different metabolic pathways, but also plays an important role in inflammation, cell proliferation, differentiation, apoptosis, and cancer growth. FXR is now recognized as a key component in the regulation of various digestive diseases such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD). In recent years, significant progress has been made in the development of agonists and antagonists targeting FXR, but their clinical application still faces the challenge of balancing efficacy and safety. Based on the core physiological functions of FXR in regulating bile acid metabolism, glucose-lipid homeostasis and inflammatory response, this article systematically analyzes the mechanism of action and clinical translation of novel FXR agonists and antagonists, focusing on their therapeutic potential in digestive diseases such as PSC, PBC, MASLD and IBD, and the prospective development of drugs based on the precise regulation strategy of FXR.