Exploiting Chemical Libraries, Structure, and Genomics in the Search for Kinase Inhibitors
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- Nathanael S. Gray
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Lisa Wodicka
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Andy-Mark W. H. Thunnissen
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Thea C. Norman
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Soojin Kwon
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- F. Hernan Espinoza
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- David O. Morgan
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Georjana Barnes
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Sophie LeClerc
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Laurent Meijer
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Sung-Hou Kim
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- David J. Lockhart
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
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- Peter G. Schultz
- N. S. Gray, T. C. Norman, S. Kwon, P. G. Schultz, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. L. Wodicka and D. J. Lockhart, Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA. A.-M. W. H. Thunnissen and S.-H. Kim, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720, USA. F. Hernan Espinoza and D. O. Morgan, Department of Physiology, University of California, San Francisco, CA 94143–0444,...
書誌事項
- 公開日
- 1998-07-24
- DOI
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- 10.1126/science.281.5376.533
- 公開者
- American Association for the Advancement of Science (AAAS)
この論文をさがす
説明
<jats:p> Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate–binding site of the human cyclin-dependent kinase 2 (CDK2). By iterating chemical library synthesis and biological screening, potent inhibitors of the human CDK2–cyclin A kinase complex and of <jats:italic>Saccharomyces cerevisiae</jats:italic> Cdc28p were identified. The structural basis for the binding affinity and selectivity was determined by analysis of a three-dimensional crystal structure of a CDK2-inhibitor complex. The cellular effects of these compounds were characterized in mammalian cells and yeast. In the latter case the effects were characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays. Purine libraries could provide useful tools for analyzing a variety of signaling and regulatory pathways and may lead to the development of new therapeutics. </jats:p>
収録刊行物
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- Science
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Science 281 (5376), 533-538, 1998-07-24
American Association for the Advancement of Science (AAAS)