T790米
表皮生长因子受体
突变体
表皮生长因子受体抑制剂
肺癌
癌症研究
化学
突变
半胱氨酸
药理学
医学
酶
生物化学
受体
吉非替尼
肿瘤科
基因
作者
Marcel Günther,Michael Juchum,Gerhard Kelter,H.H. Fiebig,Stefan Laufer
标识
DOI:10.1002/anie.201603736
摘要
The treatment of non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors is made challenging by acquired resistance caused by somatic mutations. Third-generation EGFR inhibitors have been designed to overcome resistance through covalent binding to the Cys 797 residue of the enzyme, and these inhibitors are effective against most clinically relevant EGFR mutants. However, the high dependence of these recent EGFR inhibitors on this particular interaction means that additional mutation of Cys 797 results in poor inhibitory activity, which leads to tumor relapse in initially responding patients. A new generation of irreversible and reversible mutant EGFR inhibitors was developed with strong noncovalent binding properties, and these compounds show high inhibitory activities against the cysteine-mutated L858R/T790M/C797S EGFR.
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