TY - JOUR
T1 - Discovery of new FXR agonists based on 6-ECDCA binding properties by virtual screening and molecular docking
AU - Giancristofaro, Antonella
AU - Barbosa, Arménio J. M.
AU - Ammazzalorso, Alessandra
AU - Amoia, Pasquale
AU - De Filippis, Barbara
AU - Fantacuzzi, Marialuigia
AU - Giampietro, Letizia
AU - Maccallini, Cristina
AU - Amoroso, Rosa
N1 - SFRH/BPD/112543/2015#
The study was supported by FAR funds from the Ministry of Education, University and Research (MIUR) of Italy. A. J. M. Barbosa was supported by the Post-Doc fellowship SFRH/BPD/112543/2015, FCT/MCTES, Portugal. Thanks are due to Dr. Alberto Del Rio for helpful discussions and to prof. Antonio Moschetta for the FXR plasmids.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055292640&partnerID=8YFLogxK
U2 - 10.1039/c8md00272j
DO - 10.1039/c8md00272j
M3 - Article
C2 - 30393515
AN - SCOPUS:85055292640
SN - 2040-2503
VL - 9
SP - 1630
EP - 1638
JO - MedChemComm
JF - MedChemComm
IS - 10
ER -
