Skip to main content
Log in

The why and how of phenotypic small-molecule screens

  • Commentary
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

Small-molecule phenotypic screening has high potential in the discovery of new chemical probes and new biological small-molecule targets. This commentary will discuss the basic principles underlying the design of phenotypic screens and propose some guidelines to facilitate the discovery of small molecules from phenotypic screens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Swinney, D.C. & Anthony, J. Nat. Rev. Drug Discov. 10, 507–519 (2011).

    Article  CAS  Google Scholar 

  2. Castoreno, A.B. & Eggert, U.S. ACS Chem. Biol. 6, 86–94 (2011).

    Article  CAS  Google Scholar 

  3. Rix, U. & Superti-Furga, G. Nat. Chem. Biol. 5, 616–624 (2009).

    Article  CAS  Google Scholar 

  4. Chidley, C. et al. Chimia 65, 720–724 (2011).

    Article  CAS  Google Scholar 

  5. Gregori-Puigjané, E. et al. Proc. Natl. Acad. Sci. USA 109, 11178–11183 (2012).

    Article  Google Scholar 

  6. Schenone, M., Dančík, V., Wagner, B.K. & Clemons, P.A. Nat. Chem. Biol. 9, 232–240 (2013).

    Article  CAS  Google Scholar 

  7. Eggert, U.S., Field, C.M. & Mitchison, T.J. Mol. Biosyst. 2, 93–96 (2006).

    Article  CAS  Google Scholar 

  8. Macia, E. et al. Dev. Cell 10, 839–850 (2006).

    Article  CAS  Google Scholar 

  9. von Kleist, L. et al. Cell 146, 471–484 (2011); erratum 146, 841 (2011).

    Article  CAS  Google Scholar 

  10. Zhang, X. et al. Proc. Natl. Acad. Sci. USA 109, 12485–12490 (2012).

    Article  CAS  Google Scholar 

  11. Lippincott-Schwartz, J. et al. Cell 67, 601–616 (1991).

    Article  CAS  Google Scholar 

  12. Lippincott-Schwartz, J. et al. Cell 60, 821–836 (1990).

    Article  CAS  Google Scholar 

  13. Lippincott-Schwartz, J., Yuan, L.C., Bonifacino, J.S. & Klausner, R.D. Cell 56, 801–813 (1989).

    Article  CAS  Google Scholar 

  14. Peyroche, A. et al. Mol. Cell 3, 275–285 (1999).

    Article  CAS  Google Scholar 

  15. Sata, M., Moss, J. & Vaughan, M. Proc. Natl. Acad. Sci. USA 96, 2752–2757 (1999).

    Article  CAS  Google Scholar 

  16. Mayer, T.U. et al. Science 286, 971–974 (1999).

    Article  CAS  Google Scholar 

  17. Castoreno, A.B. et al. Nat. Chem. Biol. 6, 457–463 (2010).

    Article  CAS  Google Scholar 

  18. Frye, S.V. Nat. Chem. Biol. 6, 159–161 (2010).

    Article  CAS  Google Scholar 

  19. Owen, S.C., Doak, A.K., Wassam, P., Shoichet, M.S. & Shoichet, B.K. ACS Chem. Biol. 7, 1429–1435 (2012).

    Article  CAS  Google Scholar 

  20. Edwards, A.M., Bountra, C., Kerr, D.J. & Willson, T.M. Nat. Chem. Biol. 5, 436–440 (2009).

    Article  CAS  Google Scholar 

  21. Edwards, A.M. et al. Nature 470, 163–165 (2011).

    Article  CAS  Google Scholar 

  22. Tamura, G., Ando, K., Suzuki, S., Takatsuki, A. & Arima, K. J. Antibiot. (Tokyo) 21, 160–161 (1968).

    Article  CAS  Google Scholar 

  23. Peterson, J.R. & Mitchison, T.J. Chem. Biol. 9, 1275–1285 (2002).

    Article  CAS  Google Scholar 

  24. Maliga, Z., Kapoor, T.M. & Mitchison, T.J. Chem. Biol. 9, 989–996 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank C. Shamu (Institute of Chemistry and Cell Biology–Longwood, Harvard Medical School), M. Houslay (King's College London) and members of my laboratory for helpful discussions and comments on the manuscript. Research in my laboratory is funded by US National Institutes of Health grant R01 GM082834, a Human Frontier Science Program Young Investigator Award, Marie Curie Career Integration Grant no. 304137 and European Research Council Starting Grant 306659.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ulrike S Eggert.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eggert, U. The why and how of phenotypic small-molecule screens. Nat Chem Biol 9, 206–209 (2013). https://doi.org/10.1038/nchembio.1206

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.1206

  • Springer Nature America, Inc.

This article is cited by

Navigation