UNLOCKING THE UNTARGETED KINOME WITH CHEMICAL PROTEOMICS

Project Members:	Susan Käger, Stephanie Heinzlmeir, Huichao Qiao, Dominic Helm
Cooperation:	Stefan Knapp, Oxford, Roche, GSK
Contact:	kuster[at]tum.de

While kinase inhibitors constitute a large part of the pharmacopeia (25 approved drugs, 250 in phase I-III), particularly for the treatment of cancers, the promiscuity of these molecules constitutes both an issue and an opportunity. Academic groups and the pharmaceutical industry aim to identify and develop selective inhibitors as well as compounds utilizing advantages of polypharmacology such as combination therapy and drug repurposing. Panel screenings with recombinant proteins which are traditionally used to profile the off-target activity of a molecule cannot encompass the complexity of the native kinome. Our kinobeads technology can overcome this limitation and will be used in this project to systematically profile all available clinical kinase inhibitors as well as optimized molecules from partner pharmaceutical companies, resulting in a large unbiased profiling of 1000 potent kinase inhibitors. This matrix will identify molecules which target up-to-now untargeted kinases and thus expand the repertoire of tools to study the chemical biology of disease relevant kinases.