Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors
- Author(s)
- Floriane Montanari, Anna Cseke, Katrin Wlcek, Gerhard Ecker
- 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.
- Organisation(s)
- Journal
- Journal of Biomolecular Screening
- Volume
- 22
- Pages
- 86-93
- No. of pages
- 8
- ISSN
- 1087-0571
- DOI
- https://doi.org/10.1177/1087057116657513
- Publication date
- 01-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301206 Pharmacology, 102001 Artificial intelligence
- Keywords
- ASJC Scopus subject areas
- Drug Discovery, Analytical Chemistry, Molecular Medicine, Biochemistry, Biotechnology, Pharmacology
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/virtual-screening-of-drugbank-reveals-two-drugs-as-new-bcrp-inhibitors(72e5d9d4-d159-42d1-8037-ca5f95291da2).html