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A public-private partnership to unlock the untargeted kinome

Nature Chemical Biology volume 9, pages 3–6 (2013)Cite this article

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Chemical probes are urgently needed to functionally annotate hitherto-untargeted kinases and stimulate new drug discovery efforts to address unmet medical needs. The size of the human kinome combined with the high cost associated with probe generation severely limits access to new probes. We propose a large-scale public-private partnership as a new approach that offers economies of scale, minimized redundancy and sharing of risk and cost.

Human kinases are pharmacologically tractable proteins that have essential roles in most, if not all, cellular signaling. Despite their central role in biology and their sizeable potential as therapeutic targets, only a small fraction of the 518 human protein kinases have been functionally annotated with 'selective' small-molecule inhibitors1. As of September 2012, 15 kinase inhibitors and 5 antibodies have been approved as drugs in the USA, involving merely nine different kinases as primary targets, according to the US National Cancer Institute (http://cancer.gov/cancertopics/druginfo/alphalist/). Some scientists believe that most of the therapeutically relevant kinases have been studied, but numerous lines of biological evidence strongly suggest that the unexplored kinome contains new opportunities to address unmet medical needs in cancer, metabolism, inflammation and other diseases1.

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Figure 1: Value chain of kinase inhibitors based on validation for biological investigations.

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Authors and Affiliations

  1. Stefan Knapp is in the Department of Clinical Pharmacology, and the Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK, Structural Genomics Consortium, University of Oxford, Oxford, UK.,

    Stefan Knapp

  2. Paulo Arruda and Paulo Mazzafera are in the Institute of Biology at the State University of Campinas, Campinas, Brazil.,

    Paulo Arruda & Paulo Mazzafera

  3. Division of Cancer Therapeutics, Julian Blagg and Paul Workman are in the Cancer Research UK Cancer Therapeutics Unit, the Institute of Cancer Research, London, UK.,

    Julian Blagg & Paul Workman

  4. Stephen Burley is in the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California–San Diego, San Diego, California, USA.,

    Stephen Burley

  5. Aled Edwards is at the Structural Genomics Consortium, Toronto, Ontario, Canada.,

    Aled Edwards

  6. Doriano Fabbro is with the Expertise Platform Kinases, Novartis, Basel, Switzerland.,

    Doriano Fabbro

  7. Nathanael S. Gray is at the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,

    Nathanael S Gray

  8. Bernhard Kuster is at Technische Universität München, München, Germany.,

    Bernhard Kuster

  9. Karen E. Lackey and Paul Gillespie are at Pharmaceutical Research and Early Development, Hoffmann–La Roche, Nutley, New Jersey, USA.,

    Paul Gillespie & Karen E Lackey

  10. Nicholas C.O. Tomkinson is at the University of Strathclyde, Glasgow, UK.,

    Nicholas C O Tomkinson

  11. Timothy M. Willson and William J. Zuercher are in the Department of Chemical Biology at GlaxoSmithKline, David H. Drewry, Research Triangle Park, North Carolina, USA.,

    David H Drewry, Timothy M Willson & William J Zuercher

Authors
  1. Stefan Knapp
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  2. Paulo Arruda
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  3. Julian Blagg
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  4. Stephen Burley
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  5. David H Drewry
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  6. Aled Edwards
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  7. Doriano Fabbro
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  8. Paul Gillespie
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  9. Nathanael S Gray
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  10. Bernhard Kuster
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  11. Karen E Lackey
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  12. Paulo Mazzafera
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  13. Nicholas C O Tomkinson
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  14. Timothy M Willson
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  15. Paul Workman
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  16. William J Zuercher
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Corresponding author

Correspondence to William J Zuercher.

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Competing interests

S.K. and A.E. are in the Structural Genomics Consortium, an organization that is funded in part to generate research tools and place them in the public domain without restriction on use. J.B. and P.W. are employees of the Institute of Cancer Research, which has a commercial interest in inhibitors of several kinases. P.W. has relevant commercial interactions with Piramed Pharma, Genentech, Chroma Therapeutics, Sareum, Cyclacel, Astex Pharmaceuticals and AstraZeneca.

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Knapp, S., Arruda, P., Blagg, J. et al. A public-private partnership to unlock the untargeted kinome. Nat Chem Biol 9, 3–6 (2013). https://doi.org/10.1038/nchembio.1113

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