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Faculty of 1000 evaluation for Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity
[dataset]
2007
F1000 - Post-publication peer review of the biomedical literature
unpublished
Mutations in the EGFR kinase are a cause of non-small cell lung cancer. To understand their mechanism of activation and effects on drug binding, we studied the kinetics of the L858R and G719S mutants and determined their crystal structures with inhibitors including gefitinib, AEE788 and a staurosporine. We find that the mutations activate the kinase by disrupting autoinhibitory interactions, and that they accelerate catalysis as much as 50-fold in vitro. Structures of inhibitors in complex with
doi:10.3410/f.1070897.523848
fatcat:cr6djyqjxzfojp6ybodi33leye