Susan Klaeger, Stephanie Heinzlmeir, Mathias Wilhelm, Harald Polzer, Binje Vick, Paul-Albert Koenig, Maria Reinecke, Benjamin Ruprecht, Svenja Petzoldt, Chen Meng, Jana Zecha, Katrin Reiter, Huichao Qiao, Dominic Helm, Heiner Koch, Melanie Schoof, Giulia Canevari, Elena Casale, Stefania Re Depaolini, Annette Feuchtinger, Zhixiang Wu, Tobias Schmidt, Lars Rueckert, Wilhelm Becker, Jan Huenges, Anne-Kathrin Garz, Bjoern-Oliver Gohlke, Daniel Paul Zolg, Gian Kayser, Tonu Vooder, Robert Preissner, Hannes Hahne, Neeme Tõnisson, Karl Kramer, Katharina Götze, Florian Bassermann, Judith Schlegl, Hans-Christian Ehrlich, Stephan Aiche, Axel Walch, Philipp A Greif, Sabine Schneider, Eduard Rudolf Felder, Juergen Ruland, Guillaume Médard, Irmela Jeremias, Karsten Spiekermann, Bernhard Kuster
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments...
December 1, 2017: Science