• Open Access

Annotating Human P-Glycoprotein Bioassay Data

Authors

  • Barbara Zdrazil,

    1. University of Vienna, Department of Medicinal Chemistry, Pharmacoinformatics Research Group, Althanstrasse 14, 1090 Vienna, Austria' phone/fax: +43-1-4277-55110/+43-1-4277-9551
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  • Marta Pinto,

    1. University of Vienna, Department of Medicinal Chemistry, Pharmacoinformatics Research Group, Althanstrasse 14, 1090 Vienna, Austria' phone/fax: +43-1-4277-55110/+43-1-4277-9551
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  • Poongavanam Vasanthanathan,

    1. University of Vienna, Department of Medicinal Chemistry, Pharmacoinformatics Research Group, Althanstrasse 14, 1090 Vienna, Austria' phone/fax: +43-1-4277-55110/+43-1-4277-9551
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  • Antony J. Williams,

    1. Royal Society of Chemistry, 904 Tamaras Circle, Wake Forest, NC 27587, USA
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  • Linda Zander Balderud,

    1. Discovery Sciences, Computational Sciences, AstraZeneca R&D, Mölndal, Sweden
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  • Ola Engkvist,

    1. Discovery Sciences, Computational Sciences, AstraZeneca R&D, Mölndal, Sweden
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  • Christine Chichester,

    1. Swiss Institute of Bioinformatics, CALIPHO Group, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland
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  • Anne Hersey,

    1. European Molecular Biology Laboratory (EMBL)-European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
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  • John P. Overington,

    1. European Molecular Biology Laboratory (EMBL)-European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
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  • Gerhard F. Ecker

    Corresponding author
    1. University of Vienna, Department of Medicinal Chemistry, Pharmacoinformatics Research Group, Althanstrasse 14, 1090 Vienna, Austria' phone/fax: +43-1-4277-55110/+43-1-4277-9551
    • University of Vienna, Department of Medicinal Chemistry, Pharmacoinformatics Research Group, Althanstrasse 14, 1090 Vienna, Austria' phone/fax: +43-1-4277-55110/+43-1-4277-9551
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Abstract

Huge amounts of small compound bioactivity data have been entering the public domain as a consequence of open innovation initiatives. It is now the time to carefully analyse existing bioassay data and give it a systematic structure. Our study aims to annotate prominent in vitro assays used for the determination of bioactivities of human P-glycoprotein inhibitors and substrates as they are represented in the ChEMBL and TP-search open source databases. Furthermore, the ability of data, determined in different assays, to be combined with each other is explored. As a result of this study, it is suggested that for inhibitors of human P-glycoprotein it is possible to combine data coming from the same assay type, if the cell lines used are also identical and the fluorescent or radiolabeled substrate have overlapping binding sites. In addition, it demonstrates that there is a need for larger chemical diverse datasets that have been measured in a panel of different assays. This would certainly alleviate the search for other inter-correlations between bioactivity data yielded by different assay setups.

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