A new screening assay for allosteric inhibitors of cSrc.

Article Details

Citation

Copy to clipboard

Simard JR, Kluter S, Grutter C, Getlik M, Rabiller M, Rode HB, Rauh D

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.

PubMed ID

19396179 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-naphthalen-1-ylurea	Mitogen-activated protein kinase 14	Kd (nM)	12	N/A	N/A	Details
Dasatinib	Mitogen-activated protein kinase 14	Kd (nM)	495	N/A	N/A	Details