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Farnesoid X receptor (FXR) agonists and antagonists act on a nuclear receptor that senses bile acids. In 1999 three groups identified bile acids such as chenodeoxycholic acid as endogenous FXR ligands. FXR is expressed mainly in liver, intestine and kidney, where it controls bile acid synthesis, transport and enterohepatic circulation. Activated FXR induces small heterodimer partner, which represses cholesterol 7α-hydroxylase, the rate-limiting enzyme of bile acid synthesis. FXR ligands are used to study bile acid, lipid and glucose metabolism and liver fibrosis models. Steroidal agonists include obeticholic acid, a semisynthetic bile acid analog. GW4064, cilofexor and tropifexor are nonsteroidal agonists, while DY 268 serves as an FXR antagonist.
FXR agonist 9 is a selective partial agonist of the farnesoid X receptor (FXR) with an EC50 of 0.09 µM, exhibiting 75.13% maximum efficacy. This compound has demonstrated the ability to improve pathological features associated with metabolic dysfunction and steatohepatitis in mouse models induced by a high-fat diet and carbon tetrachloride. FXR agonist 9 is valuable for research into metabolic disorders and liver diseases.
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