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PDBsum entry 5j9y
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References listed in PDB file
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Key reference
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Title
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Insight into the inhibition of drug-Resistant mutants of the receptor tyrosine kinase egfr.
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Authors
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J.Engel,
C.Becker,
J.Lategahn,
M.Keul,
J.Ketzer,
T.Mühlenberg,
L.Kollipara,
C.Schultz-Fademrecht,
R.P.Zahedi,
S.Bauer,
D.Rauh.
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Ref.
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Angew Chem Int Ed Engl, 2016,
55,
10909-10912.
[DOI no: ]
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PubMed id
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Abstract
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Targeting acquired drug resistance represents the major challenge in the
treatment of EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we describe
the structure-based design, synthesis, and biological evaluation of a novel
class of covalent EGFR inhibitors that exhibit excellent inhibition of
EGFR-mutant drug-resistant cells. Protein X-ray crystallography combined with
detailed kinetic studies led to a deeper understanding of the mode of inhibition
of EGFR-T790M and provided insight into the key principles for effective
inhibition of the recently discovered tertiary mutation at EGFR-C797S.
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