Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors. (January 2017)

• Record Type: Journal Article
• Authors: Montanari, Floriane; Cseke, Anna; Wlcek, Katrin; Ecker, Gerhard F.
• Is Part Of: Journal of biomolecular screening. Volume 22:Number 1(2017)
• Page Start: 86
• Page End: 93
• Publication Date: 2017-01
• Subjects: BCRP inhibition -- virtual screening -- logistic regression -- cisapride -- roflumilast; Drugs -- Analysis -- Periodicals; Drugs -- Testing -- Periodicals; Biomolecules -- Analysis -- Periodicals; 572.36
• DOI: 10.1177/1087057116657513
• Languages: English
• ISSNs: 1087-0571

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.