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High-throughput kinase profiling as a platform for drug discovery

Nature Reviews Drug Discovery volume 7, pages 391–397 (2008)Cite this article

Abstract

To fully exploit the potential of kinases as drug targets, novel strategies for the efficient discovery of inhibitors are required. In contrast to the traditional, linear process of inhibitor discovery, high-throughput kinase profiling enables a parallel approach by interrogating compounds against hundreds of targets in a single screen. Compound potency and selectivity are determined simultaneously, providing a choice of targets to pursue that is guided by the quality of lead compounds available, rather than by target biology alone.

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Figure 1: A novel approach to kinase-inhibitor discovery.
Figure 2: Characterization and annotation of compound libraries.
Figure 3: Identification of high-quality lead compounds.
Figure 4: Scheme for identifying multitargeted yet selective inhibitors.

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Acknowledgements

We thank S. Herrgard for creating figures, N. Lydon for helpful discussions, M. Williams for suggesting this article, and W. Wierenga, S. Bhagwat, S. Keane, D. Treiber, Y. Liu and U. Eggert for their critical reading of the manuscript. The phylogenetic tree of the human kinome in Boxes 1 and 2 is used with permission from Science and Cell Signaling Technology, Inc.

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Authors and Affiliations

  1. David M. Goldstein is at Roche Palo Alto, 3431 Hillview Avenue, R6-201, Palo Alto, California 94304, USA.,

    David M. Goldstein

  2. Nathanael S. Gray is at the Dana–Farber Cancer Institute, Harvard Medical School, Seeley G. Mudd Building 628A, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.,

    Nathanael S. Gray

  3. Patrick P. Zarrinkar is at Ambit Biosciences, 4215 Sorrento Valley Boulevard, San Diego, California 92121, USA.,

    Patrick P. Zarrinkar

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  1. David M. Goldstein
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Correspondence to Patrick P. Zarrinkar.

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Competing interests

Patrick Zarrinkar is an employee of Ambit Biosciences. Nathanael Gray receives research funding from Novartis.

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Goldstein, D., Gray, N. & Zarrinkar, P. High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov 7, 391–397 (2008). https://doi.org/10.1038/nrd2541

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