Kamila Buzun
FXR agonists in liver and biliary tract diseases
2026-01-30
Subject of research. For years, liver and biliary tract diseases have been a serious problem in healthcare systems around the world. Despite significant medical progress, greater scientific knowledge, the ability to quickly diagnose many diseases, and access to newer and more advanced therapies, the availability of therapeutic options targeting the cause of many of these diseases remains insufficient. In recent years, the farnesoid X receptor has become the subject of interest of scientists studying liver and biliary tract diseases, due to its key function, which is the synthesis and transport of bile acids, based on the enterohepatic circulation mechanism. Therefore, it is essential to maintain receptor activity and, consequently, normal liver function. The development of effective and safe FXR agonists may contribute to significant progress in the treatment of many liver and biliary tract diseases.
Purpose of research. The study aimed to present the current state of knowledge on farnesoid X receptor (FXR) agonists in the treatment of liver and biliary tract diseases. This review discusses the mechanisms of action of selected compounds as well as the possibility of their application in the treatment of selected diseases.
Materials and methods. The literature review was conducted based on PubMed and Scopus databases, using the following key words: „FXR”, „farnesoid X receptor”, „FXR agonist”, „farnesoid X receptor agonist”, „FXR agonist MASLD”, „FXR agonist metabolic dysfunction-associated steatotic liver disease”, „FXR agonist MASH”, „FXR agonist metabolic dysfunction-associated steatohepatitis”, „FXR agonist PBC”, „FXR agonist primary biliary cholangitis”, „FXR agonist PSC”, „FXR agonist primary sclerosing cholangitis”, „FXR agonist ICP”, „FXR agonist intrahepatic cholestasis of pregnancy”, „FXR agonist IFALD”, „FXR agonist intestinal failure-associated liver disease”, including original papers and review articles. The study included papers on FXR agonists and their application in the treatment of selected liver and biliary tract diseases. The above-mentioned review articles were used in preparing the chapter introducing the subject of the review.
Results. Based on the literature analysis and according to the established criteria, eight compounds that are FXR agonists were selected for this paper. Among the described compounds are obeticholic acid, INT-767, tropifexor, cilofexor, vonafexor, nidufexor, ID119031166, and EDP-305. The mechanism of action of individual compounds, the results of studies conducted to date, as well as the potential of using these compounds in treating various liver or biliary tract diseases, were discussed.
Conclusions. Conducted preliminary and initial clinical studies have demonstrated that activation of FXR with synthetic or semi-synthetic agonists may provide significant therapeutic benefits in treating different liver or biliary tract diseases. By regulating the synthesis and transport of bile acids, FXR maintains hepatic homeostasis, while disruptions in its proper functioning may affect the entire body. Therefore, the development of new FXR agonists may enhance the safety and efficacy of liver and biliary tract disease treatment.
Keywords: FXR, FXR agonists, liver, liver diseases, biliary tract diseases.
© Farm Pol, 2025, 81(7): 451–463