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, access via your institution
Relevant articles
Open Access articles citing this article.
-
Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP)
Scientific Reports Open Access 20 January 2015
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Swinney, D.C. & Anthony, J. Nat. Rev. Drug Discov. 10, 507–519 (2011).
Castoreno, A.B. & Eggert, U.S. ACS Chem. Biol. 6, 86–94 (2011).
Rix, U. & Superti-Furga, G. Nat. Chem. Biol. 5, 616–624 (2009).
Chidley, C. et al. Chimia 65, 720–724 (2011).
Gregori-Puigjané, E. et al. Proc. Natl. Acad. Sci. USA 109, 11178–11183 (2012).
Schenone, M., Dančík, V., Wagner, B.K. & Clemons, P.A. Nat. Chem. Biol. 9, 232–240 (2013).
Eggert, U.S., Field, C.M. & Mitchison, T.J. Mol. Biosyst. 2, 93–96 (2006).
Macia, E. et al. Dev. Cell 10, 839–850 (2006).
von Kleist, L. et al. Cell 146, 471–484 (2011); erratum 146, 841 (2011).
Zhang, X. et al. Proc. Natl. Acad. Sci. USA 109, 12485–12490 (2012).
Lippincott-Schwartz, J. et al. Cell 67, 601–616 (1991).
Lippincott-Schwartz, J. et al. Cell 60, 821–836 (1990).
Lippincott-Schwartz, J., Yuan, L.C., Bonifacino, J.S. & Klausner, R.D. Cell 56, 801–813 (1989).
Peyroche, A. et al. Mol. Cell 3, 275–285 (1999).
Sata, M., Moss, J. & Vaughan, M. Proc. Natl. Acad. Sci. USA 96, 2752–2757 (1999).
Mayer, T.U. et al. Science 286, 971–974 (1999).
Castoreno, A.B. et al. Nat. Chem. Biol. 6, 457–463 (2010).
Frye, S.V. Nat. Chem. Biol. 6, 159–161 (2010).
Owen, S.C., Doak, A.K., Wassam, P., Shoichet, M.S. & Shoichet, B.K. ACS Chem. Biol. 7, 1429–1435 (2012).
Edwards, A.M., Bountra, C., Kerr, D.J. & Willson, T.M. Nat. Chem. Biol. 5, 436–440 (2009).
Edwards, A.M. et al. Nature 470, 163–165 (2011).
Tamura, G., Ando, K., Suzuki, S., Takatsuki, A. & Arima, K. J. Antibiot. (Tokyo) 21, 160–161 (1968).
Peterson, J.R. & Mitchison, T.J. Chem. Biol. 9, 1275–1285 (2002).
Maliga, Z., Kapoor, T.M. & Mitchison, T.J. Chem. Biol. 9, 989–996 (2002).
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
Corresponding author
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights 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
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchembio.1206
This article is cited by
-
Antileishmanial activity evaluation of thiazolidine-2,4-dione against Leishmania infantum and Leishmania braziliensis
Parasitology Research (2020)
-
A new class of HIV-1 inhibitors and the target identification via proteomic profiling
Science China Chemistry (2018)
-
Patient-derived induced pluripotent stem cells in cancer research and precision oncology
Nature Medicine (2016)
-
Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP)
Scientific Reports (2015)