Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Rethinking screening

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

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

References

  1. Druker, B.J. Nat. Med. 15, 1149–1152 (2009).

    Article  CAS  Google Scholar 

  2. Wong, S. et al. Proc. Natl. Acad. Sci. USA 101, 17456–17461 (2004).

    Article  CAS  Google Scholar 

  3. Bachovchin, D.A., Brown, S.J., Rosen, H. & Cravatt, B.F. Nat. Biotechnol. 27, 387–394 (2009).

    Article  CAS  Google Scholar 

  4. Cravatt, B.F., Wright, A.T. & Kozarich, J.W. Annu. Rev. Biochem. 77, 383–414 (2008).

    Article  CAS  Google Scholar 

  5. Zuckermann, R.N., Kerr, J.M., Kent, S.B.H. & Moos, W.H. J. Am. Chem. Soc. 114, 10646–10647 (1992).

    Article  CAS  Google Scholar 

  6. Figliozzi, G.M., Goldsmith, R., Ng, S.C., Banville, S.C. & Zuckermann, R.N. Methods Enzymol. 267, 437–447 (1996).

    Article  CAS  Google Scholar 

  7. Akritopoulou-Zanze, I., Gracias, V. & Djuric, S. Tetrahedr. Lett. 45, 8439–8441 (2004).

    Article  CAS  Google Scholar 

  8. Lin, Q. & Blackwell, H.E. Chem. Commun. (Camb.) 2884–2886 (2006).

  9. Tempest, P.A. Curr. Opin. Drug Discov. Devel. 8, 776–788 (2005).

    CAS  PubMed  Google Scholar 

  10. Sello, J.K., Andreana, P.R., Lee, D. & Schreiber, S.L. Org. Lett. 5, 4125–4127 (2003).

    Article  CAS  Google Scholar 

  11. Lam, K.S. et al. Nature 354, 82–84 (1991).

    Article  CAS  Google Scholar 

  12. Shuker, S.B., Hajduk, P.J., Meadows, R.P. & Fesik, S.W. Science 274, 1531–1534 (1996).

    Article  CAS  Google Scholar 

  13. MacBeath, G., Koehler, A.N. & Schreiber, S.L. J. Am. Chem. Soc. 121, 7967–7968 (1999).

    Article  CAS  Google Scholar 

  14. Udugamasooriya, D.G., Dineen, S.P., Brekken, R.A. & Kodadek, T. J. Am. Chem. Soc. 130, 5744–5752 (2008).

    Article  CAS  Google Scholar 

  15. Peng, L. et al. Nat. Chem. Biol. 2, 381–389 (2006).

    Article  CAS  Google Scholar 

  16. Ringe, D. Curr. Opin. Struct. Biol. 5, 825–829 (1995).

    Article  CAS  Google Scholar 

  17. Zhu, W., Williams, R.S. & Kodadek, T.A. J. Biol. Chem. 275, 32098–32105 (2000).

    Article  CAS  Google Scholar 

  18. Lim, H.-S., Archer, C.T. & Kodadek, T. J. Am. Chem. Soc. 129, 7750–7751 (2007).

    Article  CAS  Google Scholar 

  19. Lewis, W.G. et al. Angew. Chem. Int. Ed. 41, 1053–1057 (2002).

    Article  CAS  Google Scholar 

  20. Paulick, M.G. et al. J. Comb. Chem. 8, 417–426 (2006).

    Article  CAS  Google Scholar 

  21. Ohlmeyer, M.H. et al. Proc. Natl. Acad. Sci. USA 90, 10922–10926 (1993).

    Article  CAS  Google Scholar 

  22. Liu, R., Marik, J. & Lam, K.S. J. Am. Chem. Soc. 124, 7678–7680 (2002).

    Article  CAS  Google Scholar 

  23. Wrenn, S.J., Weisinger, R.M., Halpin, D.R. & Harbury, P.B. J. Am. Chem. Soc. 129, 13137–13143 (2007).

    Article  CAS  Google Scholar 

  24. Clark, M.A. et al. Nat. Chem. Biol. 5, 647–654 (2009).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  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

Authors
  1. Thomas Kodadek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Kodadek.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.303

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing