Review Article

FXR: structures, biology, and drug development for NASH and fibrosis diseases

Si-yu Tian1, Shu-ming Chen1, Cheng-xi Pan1, Yong Li1
1 The State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361005, China
Correspondence to: Yong Li:,
DOI: 10.1038/s41401-021-00849-4
Received: 5 October 2021
Accepted: 21 December 2021
Advance online: 25 February 2022


The nuclear receptor farnesoid-X-receptor (FXR) plays an essential role in bile acid, glucose, and lipid homeostasis. In the last two decades, several diseases, such as obesity, type 2 diabetes, nonalcoholic fatty liver disease, cholestasis, and chronic inflammatory diseases of the liver and intestine, have been revealed to be associated with alterations in FXR functions. FXR has become a promising therapeutic drug target, particularly for enterohepatic diseases. Despite the large number of FXR modulators reported, only obeticholic acid (OCA) has been approved for primary biliary cholangitis (PBC) therapy as FXR modulator. In this review, we summarize the structure and function of FXR, the development of FXR modulators, and the structure–activity relationships of FXR modulators. Based on the structural analysis, we discuss potential strategies for developing future therapeutic FXR modulators to overcome current limitations, providing new perspectives for enterohepatic and metabolic diseases treatment.
Keywords: nuclear receptor; farnesoid X receptor; structure–activity relationships; FXR modulators; rational drug design; liver fibrosis diseases

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