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Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants
Author(s) -
Xu Tianfeng,
Zhang Lianwen,
Xu Shilin,
Yang ChaoYie,
Luo Jinfeng,
Ding Fang,
Lu Xiaoyun,
Liu Yingxue,
Tu Zhengchao,
Li Shiliang,
Pei Duanqing,
Cai Qian,
Li Honglin,
Ren Xiaomei,
Wang Shaomeng,
Ding Ke
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201302313
Subject(s) - t790m , mutant , mutation , computer science , chemistry , computational biology , combinatorial chemistry , cancer research , biochemistry , biology , gene , kras
Catching the mutants : Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one derivatives (see example) were identified as specific inhibitors of EGFR T790M mutants. The compounds bound with T790M or L858R/T790M mutants with significantly lower K d values than that with EGFR WT . They also selectively inhibited EGFR signal transduction and proliferation of NSCLC cells harboring EGFR L858R/T790M mutation, but were significantly less potent to cells with EGFR WT .