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PDBsum entry 5edr
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Transferase/transferase inhibitor
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PDB id
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5edr
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References listed in PDB file
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Key reference
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Title
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4-Aminoindazolyl-Dihydrofuro[3,4-D]pyrimidines as non-Covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase.
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Authors
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E.J.Hanan,
M.Baumgardner,
M.C.Bryan,
Y.Chen,
C.Eigenbrot,
P.Fan,
X.H.Gu,
H.La,
S.Malek,
H.E.Purkey,
G.Schaefer,
S.Schmidt,
S.Sideris,
I.Yen,
C.Yu,
T.P.Heffron.
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Ref.
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Bioorg Med Chem Lett, 2016,
26,
534-539.
[DOI no: ]
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PubMed id
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Abstract
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The treatment of epidermal growth factor receptor (EGFR)-driven non-small cell
lung cancers with the T790M resistance mutation remains a significant unmet
medical need. We report the identification of
4-aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of
EGFR, with excellent activity against the T790M resistance double mutants and
initial single activating mutants. Using an optimization strategy focused on
structure-based design and improving PK properties through metabolite
identification, we obtained advanced leads with high oral exposure.
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