Article

An SH3-binding allosteric modulator stabilizes the global conformation of the AML-associated Src-family kinase, Hck

2024-11-08

Abstract excerpt

While ATP-site inhibitors for protein-tyrosine kinases are often effective drugs, their clinical utility can be limited by off-target activity and acquired resistance mutations due to the conserved nature of the ATP-binding site. However, combining ATP-site and allosteric kinase inhibitors can overcome these shortcomings in a double-drugging framework. Here we explored the allosteric effects of two pyrimidine diam...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 815bd1ac-4a7f-5ed7-8821-3c39a1562a6a
DOI: 10.1101/2024.11.05.622136

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

An SH3-binding allosteric modulator stabilizes the global conformation of the AML-associated Src-family kinase, HckDOI 10.1101/2024.11.05.622136Read

Targeting SHP2 Cryptic Allosteric Sites for Effective Cancer Therapy.Semantic proximity Read

LRRK2 dynamics analysis identifies allosteric control of the crosstalk between its catalytic domains.Semantic proximity Read

The allosteric landscape of the Src kinase.Semantic proximity Read

Two helices control the dynamic crosstalk between the catalytic domains of LRRK2Semantic proximity Read

Allosteric network of dynamic coupling within BAP1-UCH revealed by methyl NMR.Semantic proximity Read

Profiling of the drug resistance of thousands of Src tyrosine kinase mutants uncovers a regulatory network that couples autoinhibition to catalytic domain dynamicsSemantic proximity Read

Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinasesSemantic proximity Read

Dynamic Allostery in PLCγ1 and Its Modulation by a Cancer Mutation Revealed by MD Simulation and NMR.Semantic proximity Read

A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in VivoSemantic proximity Read

Conservation and divergence in the allosteric architectures of five human protein kinasesSemantic proximity Read

Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity ProbesSemantic proximity Read

Specific CLK Inhibitors from a Novel Chemotype for Regulation of Alternative SplicingSemantic proximity Read