Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

HTS explorer

  • Christoph Müller1,
  • Isabella Feierberg1,
  • Ola Engkvist1 and
  • Christian Tyrchan1
Journal of Cheminformatics20146(Suppl 1):P20

https://doi.org/10.1186/1758-2946-6-S1-P20

Published: 11 March 2014

In the early stages of a drug discovery project it is often necessary to narrow down the search space for potential new leads substantially [1, 2]. This crucial step identifies a set of molecules (a hit series) that have a high likelihood of being relevant to the drug discovery project. In many cases high throughput screening (HTS) is used to test (in-vitro) large amounts of molecules against a biological target in order to validate a molecule’s potential to interact with the target and therewith its relevance to the drug discovery process. Since there are time and money constraints associated with such a process, it is not feasible to pipe the full HTS compound set through very detailed testing. Rather, an HTS process consists of several stages: a primary (spot test, SP) stage, a confirmation (retest) stage and a concentration-response (CR) stage. The later is the most resource-intensive where compounds are tested at a range of different concentrations, which allows for curve-fitting and determination of the potencies.

The HTS Explorer enables HTS evaluators across AstraZeneca R&D sites to do a comprehensive and effective screening analysis for compound prioritization within a single tool. This tool is provided as an extension to the visualization platform TIBCO Spotfire [3]. The use of Spotfire as a platform streamlines the process for the HTS evaluator and facilitates distribution of the tool as sharing of the HTS data evaluations. Further new approaches and methods can be made easily and readily available across AZ. Data is retrieved by calling PipelinePilot protocols, various web-services and queries to in-house databases [4, 5]. The main features include many different options for clustering of compounds as well as commenting on clusters, cluster visualization, prioritization and interactive reclustering. Further it enables compound annotation with e.g. the known Structure-Activity Relationship (SAR) space and offers different types of structural searches in internal and external databases.

Authors’ Affiliations

(1)
AstraZeneca R&D, Discovery Sciences Chemistry Innovation Centre & RIA iMed Medicinal Chemistry

References

  1. Cox PB, Gregg R, Vasudevan A: Abbott physicochemical tiering (APT)–A unified approach to HTS triage. Bioorg Med Chem. 2012, 20 (14): 4564-4573. 10.1016/j.bmc.2012.05.047.View ArticleGoogle Scholar
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  3. [http://spotfire.tibco.com/]
  4. Muresan S, Petrov P, Southan C, Kjellberg MJ, Kogej T, Tyrchan C, Varkonyi P, Hongxing-Xie P: Making every SAR point count: The development of Chemistry Connect for the large-scale integration of structure and bioactivity data. Drug Discov Today. 2011, 16 (23-24): 1019-1030. 10.1016/j.drudis.2011.10.005.View ArticleGoogle Scholar
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Copyright

© Müller et al; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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