Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors

Authors/others:Montanari, Floriane; Cseke, Anna; Wlcek, Katrin; Ecker, Gerhard
Abstract:The breast cancer resistance protein (BCRP) is an ABC transporter playing a crucial role in the pharmacokinetics of drugs. The early identification of substrates and inhibitors of this efflux transporter can help to prevent or foresee drug-drug interactions. In this work, we built a ligand-based in silico classification model to predict the inhibitory potential of drugs toward BCRP. The model was applied as a virtual screening technique to identify potential inhibitors among the small-molecules subset of DrugBank. Ten compounds were selected and tested for their capacity to inhibit mitoxantrone efflux in BCRP-expressing PLB985 cells. Results identified cisapride (IC50 = 0.4 µM) and roflumilast (IC50 = 0.9 µM) as two new BCRP inhibitors. The in silico strategy proved useful to prefilter potential drug-drug interaction perpetrators among a database of small molecules and can reduce the amount of compounds to test.
Date of publication:7.2016
Journal title:Journal of Biomolecular Screening
Peer reviewed:true
Digital Object Identifier (DOI):
Publication Type:Article