National Center for
3F3U: Kinase Domain Of Csrc In Complex With Inhibitor Rl37 (Type Iii)
Nat. Chem. Biol. (2009) 5 p.394-396
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.