Deposition Author(s): Gruetter, C., Klueter, S., Getlik, M., Rauh, D.
Simard, J.R., Kluter, S., Grutter, C., Getlik, M., Rabiller, M., Rode, H.B., Rauh, D.
Targeting kinases outside the highly conserved ATP pocket is thought to be a promising strategy for overcoming bottlenecks in kinase inhibitor research, such as limited selectivity and drug resistance. Here we report the development and application of a direct binding assay to detect small molecules that stabilize the inactive conformation of the tyrosine kinase cSrc. Protein X-ray crystallography validated the assay results and confirmed an exclusively allosteric binding mode.
Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.