化学
变构调节
T790米
立体化学
表皮生长因子受体抑制剂
激酶
药理学
对接(动物)
突变体
喹唑啉
生物化学
表皮生长因子受体
酶
受体
医学
吉非替尼
护理部
基因
作者
Mengmeng Fan,Liping Hu,Shengmin Shi,Xiaomeng Song,Huan He,Baohui Qi
标识
DOI:10.1016/j.bmc.2023.117534
摘要
Acquired drug resistance occurred in the treatment of non-small-cell lung cancer is a persistent challenge, especially in EGFR mutant type. In this study, we present design, synthesis and biological evaluation of novel quinazoline and pyrrolopyrimidine derivatives that simultaneously occupy the orthosteric and allosteric sites of EGFR. Among them, compound A-7 was confirmed as a potential EGFRL858R/T790M/C797S and EGFRDel19/T790M/C797S inhibitor. Docking study indicated that compound A-7 could simultaneously occupy two binding sites of EGFR and form three key H-bonds with the residues Met793, Lys745 and Met766 in two regions.
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