Introduction: The Farnesoid X receptor (FXR) is a key transcription factor that is involved in the bile acid signaling network. The modulation of the FXR activity influences glucose and lipid homeostasis, reduces obesity and insulin resistance, as well as it regulates the pathogenesis of inflammatory and metabolic disorders. FXR ligands have therefore emerged in drug discovery as promising therapeutic agents for the prevention and treatment of gastrointestinal and liver diseases, including cancer.
Areas covered: Recent advances in the field of FXR modulators are reviewed, with a particular attention on patent applications filed in the past 5 years related to both the discovery and development of FXR targeting drugs.
Expert opinion: FXR agonists have proven their efficacy and safety in humans and have shown a significant potential as clinical agents to treat metabolic and inflammatory associated conditions. However, several challenges, including adverse events such as pruritus, remain to be solved. Current studies aim to gain insights into the pathophysiological mechanisms by which FXR regulates metabolism and inflammation in terms of tissue/organ/isoform-specificity, post-translational modifications and coregulatory proteins, on the route of novel, improved FXR modulators.
Keywords: Bile acids; Farnesoid X receptor; cancer; nonalcoholic fatty liver diseases; primary biliary cirrhosis; process chemistry; steatohepatitis; structure–activity relationships.