Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors

Marcus Bantscheff, Dirk Eberhard, Yann Abraham, Sonja Bastuck, Markus Boesche, Scott Hobson, Toby Mathieson, Jessica Perrin, Manfred Raida, Christina Rau, Valérie Reader, Gavain Sweetman, Andreas Bauer, Tewis Bouwmeester, Carsten Hopf, Ulrich Kruse, Gitte Neubauer, Nigel Ramsden, Jens Rick, Bernhard KusterGerard Drewes

Research output: Contribution to journalArticlepeer-review

901 Scopus citations


We describe a chemical proteomics approach to profile the interaction of small molecules with hundreds of endogenously expressed protein kinases and purine-binding proteins. This subproteome is captured by immobilized nonselective kinase inhibitors (kinobeads), and the bound proteins are quantified in parallel by mass spectrometry using isobaric tags for relative and absolute quantification (iTRAQ). By measuring the competition with the affinity matrix, we assess the binding of drugs to their targets in cell lysates and in cells. By mapping drug-induced changes in the phosphorylation state of the captured proteome, we also analyze signaling pathways downstream of target kinases. Quantitative profiling of the drugs imatinib (Gleevec), dasatinib (Sprycel) and bosutinib in K562 cells confirms known targets including ABL and SRC family kinases and identifies the receptor tyrosine kinase DDR1 and the oxidoreductase NQO2 as novel targets of imatinib. The data suggest that our approach is a valuable tool for drug discovery.

Original languageEnglish
Pages (from-to)1035-1044
Number of pages10
JournalNature Biotechnology
Issue number9
StatePublished - Sep 2007
Externally publishedYes


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