A new screening assay for allosteric inhibitors of cSrc

Jeffrey R Simard; Sabine Klüter; Christian Grütter; Matthäus Getlik; Matthias Rabiller; Haridas B Rode; Daniel Rauh

doi:10.1038/nchembio.162

A new screening assay for allosteric inhibitors of cSrc

Nat Chem Biol. 2009 Jun;5(6):394-6. doi: 10.1038/nchembio.162. Epub 2009 Apr 26.

Authors

Jeffrey R Simard¹, Sabine Klüter, Christian Grütter, Matthäus Getlik, Matthias Rabiller, Haridas B Rode, Daniel Rauh

Affiliation

¹ Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.

PMID: 19396179
DOI: 10.1038/nchembio.162

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Allosteric Regulation*
Binding Sites
Crystallography, X-Ray
Hydrogen Bonding
Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors*
Proto-Oncogene Proteins pp60(c-src) / metabolism

Substances

Adenosine Triphosphate
Proto-Oncogene Proteins pp60(c-src)

Associated data

PubChem-Substance/57551943
PubChem-Substance/57551944
PubChem-Substance/57551945
PubChem-Substance/57551946
PubChem-Substance/57551947
PubChem-Substance/57551948
PubChem-Substance/57551949
PubChem-Substance/57551950
PubChem-Substance/57551951
PubChem-Substance/57551952
PubChem-Substance/57551953
PubChem-Substance/57551954
PubChem-Substance/57551955
PubChem-Substance/57551956
PubChem-Substance/57551957