化学
T790米
苯胺
IC50型
突变体
立体化学
酶
铅化合物
激酶
结构-活动关系
野生型
效力
体外
突变
生物化学
有机化学
基因
克拉斯
作者
Anran Song,Jianbin Zhang,Ge Yang,Changyuan Wang,Qiang Meng,Zeyao Tang,Jinyong Peng,Kexin Liu,Yanxia Li,Xiaodong Ma
标识
DOI:10.1016/j.bmc.2017.03.032
摘要
With the aim to overcome the drug resistance induced by the EGFR T790M mutation (EGFRT790M), herein, a family of diphenylpyrimidine derivatives (Sty-DPPYs) bearing a C-2 (E)-4-(styryl)aniline functionality were designed and synthesized as potential EGFRT790M inhibitors. Among them, the compound 10e displayed strong potency against the EGFRT790M enzyme, with the IC50 of 11.0nM. Compound 10e also showed a higher SI value (SI=49.0) than rociletinib (SI=21.4), indicating its less side effect. In addition, compound 10e could effectively inhibit the proliferation of H1975 cells harboring the EGFRT790M mutation, within the concentration of 2.91μM. Significantly, compound 10e has low toxicity against the normal HBE cell (IC50=22.48μM). This work provided new insights into the discovery of potent and selective inhibitor against EGFRT790M over wild-type (EGFRWT).
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