Kinase Inhibitor Profiling Using Chemoproteomics

  • Markus SchirleEmail author
  • Eugene C. Petrella
  • Scott M. Brittain
  • David Schwalb
  • Edmund Harrington
  • Ivan Cornella-Taracido
  • John A. Tallarico
Part of the Methods in Molecular Biology book series (MIMB, volume 795)


Quantitative chemoproteomics has recently emerged as an experimental approach to determine protein interaction profiles of small molecules in a given cell line or tissue. In contrast to standard biochemical and biophysical kinase assays, application of this method to kinase inhibitors determines compound binding to endogenously expressed kinases under conditions approximating the physiological situation with regard to the molecular state of the kinase and presence of required cofactors and regulatory proteins. Using a dose-dependent, competition-based experimental design in combination with quantitative mass spectrometry approaches, such as the use of tandem mass tags (TMT) for isobaric labeling described here, allows to rank-order interactions of inhibitors to kinase by binding affinity.

Key words

Chemoproteomics Quantitative proteomics Target identification Isobaric mass tags 



We thank Heather Contant and Lindsay Nolitt for expert technical assistance and John Damask and Ioannis Moutsatsos for their crucial role in building the data processing and analysis environment.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Markus Schirle
    • 1
    Email author
  • Eugene C. Petrella
    • 1
  • Scott M. Brittain
    • 1
  • David Schwalb
    • 1
  • Edmund Harrington
    • 1
  • Ivan Cornella-Taracido
    • 1
  • John A. Tallarico
    • 1
  1. 1.Novartis Institutes for Biomedical ResearchCambridgeUSA

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