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Challenges facing the biologist doing chemical genetics

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The goal of high-throughput screening (HTS) from the perspective of the biologist is to identify a highly specific small molecule that can be used to inhibit a protein in its normal biological context. Although several useful small molecules have been identified with HTS, there are many challenges to be considered when contemplating a screen, especially by those unfamiliar with chemical biology.

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Figure 1: Comparison of a traditional high-throughput screen with a screen that selects for and enriches potential lead compounds.

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Acknowledgements

The authors thank D. Halpin and J. Williams for useful discussions.

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of California, Berkeley, 94720, California, USA

    Jon Soderholm, Karsten Weis & Rebecca Heald

  2. Department of Pharmaceutical Chemistry, University of California, San Francisco, 94143, California, USA

    Mike Uehara-Bingen

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  1. Jon Soderholm
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Soderholm, J., Uehara-Bingen, M., Weis, K. et al. Challenges facing the biologist doing chemical genetics. Nat Chem Biol 2, 55–58 (2006). https://doi.org/10.1038/nchembio0206-55

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