Proteomics-based target deconvolution of clinical multi-kinase inhibitors inducing apoptosis in primary chronic lymphocytic leukemia cells (CLL)

摘要

BCLL cells and the related Ramos cell line display a remarkably different kinase expression profile. Kinobead based competition binding assay enables profiling of kinase inhibitors in patient material The method allows to establish compound potency in a close to native environment under preservation of protein complexes. Kinase complex components display matching IC_(50)s. Tyrosine kinase inhibitors are not effective in inducing apoptosis in BCLL cells. CDK inhibitors BMS-387032 and flavopiridol induce apoptosis via inhibition of CDK9.