Overview of Chemical Genomics and Proteomics

  • Edward D. ZandersEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 800)


Chemical genetics, genomics, and proteomics have been in existence as distinct offshoots of chemical biology for about 20 years. This review provides a brief definition of each, followed by some examples of how each technology is being used to advance basic research and drug discovery.

Key words

Chemical genetics Chemical genomics Chemical proteomics Connectivity map Epigenomics Affinity selection Kinases 


  1. 1.
    Leathes JB (1930) The Harveian oration on the birth of chemical biology. Br Med J 2:671–676PubMedCrossRefGoogle Scholar
  2. 2.
    MacBeath G (2001) Chemical genomics: what will it take and who gets to play? Genome Biol doi:10.1186/gb-2001-2-6-comment 2005Google Scholar
  3. 3.
    Schreiber SL (1998) Chemical genetics resulting from a passion for synthetic organic chemistry. Bioorg Med Chem 6:1127–52PubMedCrossRefGoogle Scholar
  4. 4.
    Jessani N, Liu Y, Humphrey M, Cravatt BF (2002) Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness. Proc Natl Acad Sci USA 99:10335–40PubMedCrossRefGoogle Scholar
  5. 5.
    Jeffery DA, Bogyo M (2003) Chemical proteomics and its application to drug discovery. Curr Opin Biotechnol 14:87–95PubMedCrossRefGoogle Scholar
  6. 6.
    Chen TF et al. (2000) A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR) Proc Natl Acad Sci USA 97:13227–32CrossRefGoogle Scholar
  7. 7.
    Caron P (2005) Introduction to Chemical Genomics. In: Zanders ED (ed) Chemical Genomics, Reviews and Protocols. Humana Press, New JerseyGoogle Scholar
  8. 8.
    Stockwell BR (2000) Chemical genetics: ligand-based discovery of gene function. Nat Rev Genet 1:116–25PubMedCrossRefGoogle Scholar
  9. 9.
    Rix U, Superti-Furga G (2009) Target profiling of small molecules by chemical proteomics. Nat Chem Biol 5:616–24PubMedCrossRefGoogle Scholar
  10. 10.
    Kidd D, Liu Y, Cravatt BF (2001) Profiling serine hydrolase activities in complex proteomes. Biochemistry 40:4005–15PubMedCrossRefGoogle Scholar
  11. 11.
    Hughes TR et al. (2000) Functional discovery via a compendium of expression profiles. Cell 102:109–26PubMedCrossRefGoogle Scholar
  12. 12.
    Ganter B et al. (2005) Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. J Biotechnol 119:219–44PubMedCrossRefGoogle Scholar
  13. 13.
    Lamb J (2006) The connectivity map: Using Gene-Expression Signatures to Connect Small Molecules, Genes and Disease. Science 313:1929–1935PubMedCrossRefGoogle Scholar
  14. 14.
    Subramanian A (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550PubMedCrossRefGoogle Scholar
  15. 15.
    Josset L et al. (2010) Gene expression signature-based screening identifies new broadly effective influenza A antivirals. PLoS One doi:10.1371/journal.pone.0013169Google Scholar
  16. 16.
    Hassane DC et al. (2010) Chemical genomic screening reveals synergism between parthenolide and inhibitors of the PI-3 kinase and mTOR pathways. Blood 116:5983–90PubMedCrossRefGoogle Scholar
  17. 17. Accessed 15 February 2011
  18. 18.
    Barrero MJ, Izpisua Belmonte JC (2011) Regenerating the epigenome. EMBO Rep doi:10.1038/embor.2011.10Google Scholar
  19. 19.
    Berdasco M, Esteller M (2010) Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell 19:698–711PubMedCrossRefGoogle Scholar
  20. 20.
    Eliseeva ED et al. (2007) Characterization of novel inhibitors of histone acetyltransferases. Mol Cancer Ther 6:2391–8PubMedCrossRefGoogle Scholar
  21. 21.
    M Yoshida (2009) Chemical genomics: a key to the epigenome – an interview with Minoru Yoshida. Int J Dev Biol 53: 269–74PubMedCrossRefGoogle Scholar
  22. 22.
    Kaida D et al. (2007) Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 3:533–5CrossRefGoogle Scholar
  23. 23.
    Taverna SD Cole PA (2010) Reader’s block. Nature 468:1050–1051PubMedCrossRefGoogle Scholar
  24. 24.
    Fillipakopoulos P et al. (2010) Selective inhibition of BET bromodomains. Nature 468:1067–1073CrossRefGoogle Scholar
  25. 25.
    Nicodeme E et al. (2010) Suppression of inflammation by a synthetic histone mimic. Nature 468:1119–1123PubMedCrossRefGoogle Scholar
  26. 26.
    Graves PR et al. (2002) Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol Pharmacol 62:1364–72PubMedCrossRefGoogle Scholar
  27. 27.
    Wissing J et al. (2007) Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry. Mol Cell Proteomics 6:537–47PubMedGoogle Scholar
  28. 28.
    Bantscheff M et al. (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 25:1035–44PubMedCrossRefGoogle Scholar
  29. 29.
    Peters EC, Gray NS (2007) Chemical Proteomics Identifies Unanticipated Targets of Clinical Kinase Inhibitors. ACS Chemical Biology 2:661–664PubMedCrossRefGoogle Scholar
  30. 30.
    Rix U et al. (2010) A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells INNO-406 target profile in CML. Leukemia 24:44–50PubMedCrossRefGoogle Scholar
  31. 31.
    Ito T et al. (2010) Identification of a Primary Target of Thalidomide Teratogenicity. Science 327:1345–1350PubMedCrossRefGoogle Scholar
  32. 32.
    Sakamoto S et al. (2009) Development and application of high-performance affinity beads: Toward chemical biology and drug discovery. The Chemical Record 9:66–85CrossRefGoogle Scholar
  33. 33. Accessed 16 February 2011

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.BioVillage Ltd.CambridgeUK

Personalised recommendations