Annotating Human P-Glycoprotein Bioassay Data

Author(s)
Barbara Zdrazil, Marta Pinto, Vasanthanathan Poongavanam, Antony J. Williams, Linda Zander Balderud, Ola Engkvist, Christine Chichester, Anne Hersey, John P. Overington, Gerhard Ecker
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.

Organisation(s)
External organisation(s)
Royal Society of Chemistry, AstraZeneca, Swiss Institute of Bioinformatics, European Bioinformatics Institute
Journal
Molecular Informatics
Volume
31
Pages
599-609
No. of pages
11
ISSN
1868-1743
DOI
https://doi.org/10.1002/minf.201200059
Publication date
2012
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry, 301305 Medical chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/21ed1ac3-ce76-471a-a9b8-09d9c7096731