Abstract
Erlotinib and gefitinib, tyrosine kinase inhibitors used to block EGFR (epidermal growth factor receptor) signalling in cancer, are thought to bind only the active conformation of the EGFR-TKD (tyrosine kinase domain). Through parallel computational and crystallographic studies, we show in the present study that erlotinib also binds the inactive EGFR-TKD conformation, which may have significant implications for its use in EGFR-mutated cancers.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line
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Crystallography, X-Ray
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / chemistry
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ErbB Receptors / metabolism*
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Erlotinib Hydrochloride
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Humans
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Insecta
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Protein Conformation / drug effects
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Protein Kinase Inhibitors / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Protein Structure, Tertiary / drug effects
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Quinazolines / metabolism*
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Quinazolines / pharmacology
Substances
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Protein Kinase Inhibitors
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Quinazolines
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Erlotinib Hydrochloride
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EGFR protein, human
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ErbB Receptors