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Structure-function of EGFR kinase domain and its inhibitors

  • Charles Eigenbrot
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The EGF receptor is a key mediator of oncogenic transformation in a wide variety of solid tumors. Since 2002, there has been an explosion of X-ray crystallographic results that provide powerful insight into the activation and hyperactivation of this receptor and of its close homologues HER2, HER3, and HER4. The ability to catalyze phospho-transfer resides in the EGFR intracellular tyrosine kinase domain, which has proven a clinically useful target for therapeutic intervention. The rapidly expanding catalogue of EGFR kinase domain structures is surveyed with a focus on inhibitor activities and liabilities, as well as on control and dysregulation phenomena intrinsic to the protein.

keywords:

X-ray crystallography small molecule inhibitor escape mutation kinase activation allostery L858R T790M 

Notes

Acknowledgements

Grateful acknowledgement is made to Professor M. J. Eck and to Dr. C-H Yun for access to their manuscript and coordinate files in advance of publication.

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Charles Eigenbrot
    • 1
  1. 1.Department of Protein Engineering MS 27Genentech, IncSouth San FranciscoCA

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