Recombinant Human FXR protein

The farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is a ligand-activated transcription factor primarily expressed in the liver, intestine, kidneys, and adipose tissue. Discovered in 1995. FXR plays a central role in regulating bile acid homeostasis, lipid metabolism, glucose balance, and inflammatory responses. It is activated by endogenous bile acids, such as chenodeoxycholic acid, which bind to its ligand-binding domain, triggering conformational changes that enable interaction with co-regulators and DNA response elements. Dysregulation of FXR signaling is linked to metabolic disorders (e.g., non-alcoholic fatty liver disease, diabetes), cholestasis, and certain cancers, making it a therapeutic target.

Recombinant FXR proteins are engineered using heterologous expression systems (e.g., E. coli, mammalian cells) to produce purified, functional FXR for research and drug development. These proteins retain key structural domains: a DNA-binding domain (DBD) for target gene recognition and a ligand-binding domain (LBD) for compound interaction. Recombinant FXR enables high-throughput screening of agonists/antagonists, structural studies (e.g., X-ray crystallography), and mechanistic investigations into receptor-ligand dynamics. Notably, obeticholic acid, an FXR agonist derived from such research, is approved for treating primary biliary cholangitis. Ongoing efforts focus on optimizing FXR modulators with tissue-specific activity and reduced side effects, underscoring the importance of recombinant FXR in advancing precision therapies for metabolic and hepatic diseases.