Farnesoid X receptor (FXR) modulates the expression of genes involved in
lipid and
carbohydrate homeostasis and inflammatory processes. This
nuclear receptor is likely a
tumor suppressor in several
cancers, but its molecular mechanism of suppression is still under study. Several studies reported that FXR agonism increases the survival of colorectal, biliary tract, and
liver cancer patients. In addition, FXR expression was shown to be down-regulated in many diseases such as
obesity,
irritable bowel syndrome, glomerular
inflammation, diabetes,
proteinuria, and
ulcerative colitis. Therefore, development of novel FXR agonists may have significant potential in the prevention and treatment of these diseases. In this scenario, computer-aided
drug design procedures can be resourcefully applied for the rapid identification of promising
drug candidates. In the present study, we applied the molecular docking method in conjunction with molecular dynamics (MD) simulations to find out potential agonists for FXR based on structural similarity with the
drug that is currently used as FXR agonist,
obeticholic acid. Our results showed that
alvimopan and
montelukast could be used as potent FXR activators and outperform the binding affinity of
obeticholic acid by forming stable conformation with the
protein in silico. However, further investigational studies and validations of the selected drugs are essential to figure out their suitability for preclinical and clinical trials.