A new screening assay for allosteric inhibitors of cSrc.
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.
Simard
Jeffrey R
JR
Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.
Klüter
Sabine
S
Grütter
Christian
C
Getlik
Matthäus
M
Rabiller
Matthias
M
Rode
Haridas B
HB
Rauh
Daniel
D
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
D000255:Adenosine Triphosphate; D016392:Proto-Oncogene Proteins pp60(c-src)