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

Antonella Giancristofaro, Arménio J. M. Barbosa, Alessandra Ammazzalorso, Pasquale Amoia, Barbara De Filippis, Marialuigia Fantacuzzi, Letizia Giampietro, Cristina Maccallini, Rosa Amoroso

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)1630-1638
Number of pages9
JournalMedChemComm
Volume9
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

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