Characterisation of kinase-selective inhibitors by chemical proteomics.
Low-molecular-weight inhibitors of protein kinases are extensively used as research tools in signal transduction analysis and constitute a rapidly growing class of therapeutics for targeted intervention in human diseases. To determine how kinase-selective drugs interfere with cellular physiology on the molecular level, experimental strategies relying on the affinity capture of cellular targets in combination with protein identification by mass spectrometry have been established for a variety of kinase inhibitors. Importantly, these chemical proteomic methods permit the direct analysis of kinase inhibitor selectivity in biological systems and have led to new insights into the cellular modes of action of kinase-selective small molecule antagonists.
Daub
Henrik
H
Department of Molecular Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18A, 82152 Martinried, Germany. daub@biochem.mpg.de
D000818:Animals; D002846:Chromatography, Affinity / Q000379:methods; D004353:Drug Evaluation, Preclinical; D004800:Enzymes, Immobilized / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects
D004800:Enzymes, Immobilized; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases