Discovery of new FXR agonists based on 6-ECDCA binding properties by virtual screening and molecular docking

• DOI: 10.1039/c8md00272j
• Publication Date: 2018-07-04T12:35:07Z
• Authors: Antonella Giancri...; Arménio J. M. Bar...; Alessandra Ammazz...; Pasquale Amoia; Barbara De Filippis; Marialuigia Fanta...; Letizia Giampietro; Cristina Maccallini; Rosa Amoroso
• Keywords: Docking (animal)

FXR is a member of the nuclear receptor superfamily, which regulates expression various genes involved in bile acid, lipid and glucose metabolism. Targeting with small molecules has been exploited to treat lipid-related disorders diseases such as cholestasis, gallstones hepatic disorders. In this work, we expand existing pool known agonists using fast hit-to-lead structure-based pharmacophore docking screening protocol. A set 25 was selected after large database commercial chemicals, experimental tests were carried out demonstrate their ability activate FXR. Three novel are reported, namely, one full agonist, more efficient than endogenous ligand chenodeoxycholic two partial agonists.