Large databases, for example the DrugBank database, provide information about biological activity and chemical structure of small molecules and are widely used in drug development for identification of new lead structures.
The farnesoid X receptor (FXR) is a ligand activated transcription factor involved in key regulation mechanisms within glucose and lipid homeostasis.
Although FXR became an established target in drug development for diseases associated with lipid, glucose or hepatic disorders during the last decade, none of the developed compounds have reached later phases of clinical development so far.
We used a SOM trained with known FXR ligands to screen the DrugBank database for potential ligands for FXR. In this article, we report the successful identification of six approved drugs out of the Drugbank as FXR modulators (ketoconazole, pentamidine, dobutamine, imatinib, papaverine and montelukast) by using a SOM for screening of the DrugBank database.
We show FXR modulation by selected compounds in a full length FXR transactivation assay and modulation of a FXR target gene by imatinib.