NEW CHEMICAL PROBES TO STUDY THE HUMAN KINOME

Project Members:	Xin Ku, Stephanie Heinzlmeir, Guillaume Médard
Cooperation:	Xiaofeng Liu, Shanghai
Contact:	xin.ku[at]tum.de

Immobilized inhibitors have proven an efficient tool for chemical proteomics. The kinobeads technology features kinase inhibitors covalently attached to sepharose beads for affinity kinome enrichment from cell or tissue lysates. This technology, combined with mass spectrometry, is of particular interest for the profiling of existing kinase inhibitors which often leads to the identification of new targets. For medicinal chemistry campaigns, it also provides for a 2 in 1 primary and selectivity assay. The current kinobeads enable the enrichment of a large portion of the human kinome. However, a few families of kinases are not efficiently pulled down by these kinobeads, which prevents the efficient profiling of some classes of kinase inhibitors or the study of the differential expression of these families of kinases across cell lines or tissues. This project aims at "filling the gaps" and hence at extending the advantages of this technology to profile current and future VEGFR, PDGFR and FGR inhibitors. There are known inhibitors of these families of kinases; the most promising molecules (active, unselective, linkable) will be derived to synthesize suitable probes. The probes will be tested in pull-down assays and the most promising added to the kinobeads. This obtained new generation of kinobeads will be used to profile selected inhibitors.