title: A new screening assay for allosteric inhibitors of cSrc.
abstract: 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.
authors.affiliation: Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Simard
authors.forename: Sabine
authors.initials: S
authors.lastname: Klüter
authors.forename: Christian
authors.initials: C
authors.lastname: Grütter
authors.forename: Matthäus
authors.initials: M
authors.lastname: Getlik
authors.forename: Matthias
authors.initials: M
authors.lastname: Rabiller
authors.forename: Haridas B
authors.initials: HB
authors.lastname: Rode
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D016392:Proto-Oncogene Proteins pp60(c-src)