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Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302078/ https://www.ncbi.nlm.nih.gov/pubmed/27401583 http://dx.doi.org/10.1177/1087057116657513 |
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author | Montanari, Floriane Cseke, Anna Wlcek, Katrin Ecker, Gerhard F. |
author_facet | Montanari, Floriane Cseke, Anna Wlcek, Katrin Ecker, Gerhard F. |
author_sort | Montanari, Floriane |
collection | PubMed |
description | 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 (IC(50) = 0.4 µM) and roflumilast (IC(50) = 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. |
format | Online Article Text |
id | pubmed-5302078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-53020782017-02-21 Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors Montanari, Floriane Cseke, Anna Wlcek, Katrin Ecker, Gerhard F. J Biomol Screen Original Research 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 (IC(50) = 0.4 µM) and roflumilast (IC(50) = 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. SAGE Publications 2016-07-08 2017-01 /pmc/articles/PMC5302078/ /pubmed/27401583 http://dx.doi.org/10.1177/1087057116657513 Text en © 2016 Society for Laboratory Automation and Screening http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Montanari, Floriane Cseke, Anna Wlcek, Katrin Ecker, Gerhard F. Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors |
title | Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors |
title_full | Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors |
title_fullStr | Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors |
title_full_unstemmed | Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors |
title_short | Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors |
title_sort | virtual screening of drugbank reveals two drugs as new bcrp inhibitors |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302078/ https://www.ncbi.nlm.nih.gov/pubmed/27401583 http://dx.doi.org/10.1177/1087057116657513 |
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