Navigating the kinome (original) (raw)

Nature Chemical Biology volume 7, pages 200–202 (2011)Cite this article

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Abstract

Although it is increasingly being recognized that drug-target interaction networks can be powerful tools for the interrogation of systems biology and the rational design of multitargeted drugs, there is no generalized, statistically validated approach to harmonizing sequence-dependent and pharmacology-dependent networks. Here we demonstrate the creation of a comprehensive kinome interaction network based not only on sequence comparisons but also on multiple pharmacology parameters derived from activity profiling data. The framework described for statistical interpretation of these network connections also enables rigorous investigation of chemotype-specific interaction networks, which is critical for multitargeted drug design.

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Authors and Affiliations

  1. Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois, USA
    James T Metz, Eric F Johnson, Niru B Soni, Philip J Merta, Lemma Kifle & Philip J Hajduk

Authors

  1. James T Metz
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  2. Eric F Johnson
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  3. Niru B Soni
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  4. Philip J Merta
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  5. Lemma Kifle
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  6. Philip J Hajduk
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Contributions

J.T.M. performed all of the statistical analyses and created the network visualizations; E.F.J. designed the initial kinome screening panel and supervised the enzymology; N.B.S., P.J.M. and L.K. performed all kinase assays; P.J.H. supervised the research and wrote the manuscript.

Corresponding author

Correspondence toPhilip J Hajduk.

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Competing interests

All authors are currently employed by and obtain their salary from Abbott Laboratories.

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Metz, J., Johnson, E., Soni, N. et al. Navigating the kinome.Nat Chem Biol 7, 200–202 (2011). https://doi.org/10.1038/nchembio.530

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