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Measuring and interpreting the selectivity of protein kinase inhibitors

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Journal of Chemical Biology

Abstract

Protein kinase inhibitors are a well-established class of clinically useful drugs, particularly for the treatment of cancer. Achieving inhibitor selectivity for particular protein kinases often remains a significant challenge in the development of new small molecules as drugs or as tools for chemical biology research. This review summarises the methodologies available for measuring kinase inhibitor selectivity, both in vitro and in cells. The interpretation of kinase inhibitor selectivity data is discussed, particularly with reference to the structural biology of the protein targets. Measurement and prediction of kinase inhibitor selectivity will be important for the development of new multi-targeted kinase inhibitors.

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Acknowledgments

This work was supported by The Institute of Cancer Research (studentship to L.A.S.) and Cancer Research UK grant number C309/A2874. We acknowledge NHS funding to the NHIR Biomedical Research Centre.

Conflict of interests statement

The Cancer Research UK Centre for Cancer Therapeutics is an academic reference centre for the EZReader II, Caliper Life Sciences, Inc. The authors are employees (I.C.) or students (L.A.S.) of The Institute of Cancer Research which has commercial interests in the development of kinase inhibitors. The authors (I.C.) have or have had direct or indirect commercial interactions with Astex Therapeutics Ltd, Vernalis Ltd, Sareum Ltd and AstraZeneca plc.

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  1. Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK

    Lynette A. Smyth & Ian Collins

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Correspondence to Lynette A. Smyth.

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Smyth, L.A., Collins, I. Measuring and interpreting the selectivity of protein kinase inhibitors. J Chem Biol 2, 131–151 (2009). https://doi.org/10.1007/s12154-009-0023-9

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