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Rethinking screening

Nature Chemical Biology volume 6, pages 162–165 (2010)Cite this article

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Bioactive compounds are most frequently identified via high-throughput screening campaigns. This article discusses the strengths and weaknesses of the most popular screening approaches and the utility of compounds derived from them.

There is a tremendous appetite for new pharmacological tools with which to manipulate protein function. Whereas natural product discovery remains an important activity, nowadays most new bioactive compounds are identified through high-throughput screening efforts, which used to be the purview of large pharma but are now conducted routinely in the academic world. Have these efforts had a commensurate impact on biology and medicine? What are we doing right, what are we doing wrong and how can we do better? This article provides my own perspective on these issues.

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Figure 1: Examples of chemical syntheses used for the construction of combinatorial libraries that are simple enough for non-expert chemists to carry out.
Figure 2: Discovery of peptoid ligands for an integral membrane receptor via a two-color cell binding screen VEGF receptor 2 (VEGFR2) was the target of this screen.

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Acknowledgements

I thank G. Micalizo, P. MacDonald and P. LoGrasso (Scripps Florida) for comments on the manuscript and the US National Institutes of Health (DP10D00066301) for support.

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  1. Thomas Kodadek is in the Department of Chemistry and the Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.,

    Thomas Kodadek

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Correspondence to Thomas Kodadek.

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Kodadek, T. Rethinking screening. Nat Chem Biol 6, 162–165 (2010). https://doi.org/10.1038/nchembio.303

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