Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.
Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.
复制标题
发现带有间苯二酚基序的 2,4-二芳基氨基嘧啶作为新型 ALK 抑制剂来克服 G1202R 耐药突变。
DOI：
10.1016/j.ejmech.2017.12.060
复制
发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Ao Zhang
中科院分区：
文献类型：
--
作者：
Kaijun Geng;Zongjun Xia;Yinchun Ji;Ruisi Zhang;Deqiao Sun;Jing Ai;Zilan Song;Meiyu Geng;Ao Zhang
To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G1202R is located. Compound12dturns out as the most potent with IC50values of 1.7, 3.5, and 1.8 nM against ALK wild type, gatekeeper mutant L1196M, and the G1202R mutant, respectively. More importantly, compound12dhas excellent inhibitory effects against the proliferation of BaF3 cells specifically expressing ALK wild type, gatekeeper L1196M, and the most challenging mutant G1202R, with IC50values all less than 1.5 nM. Collectively, compound12dis worthy of further investigation as a new more potent third-generation ALK inhibitor to circumvent drug resistance of both the first-generation and the second-generation inhibitors.
登录
查看更多内容
影响因子：
28.2
作者：
Friboulet L;Li N;Katayama R;Lee CC;Gainor JF;Crystal AS;Michellys PY;Awad MM;Yanagitani N;Kim S;Pferdekamper AC;Li J;Kasibhatla S;Sun F;Sun X;Hua S;McNamara P;Mahmood S;Lockerman EL;Fujita N;Nishio M;Harris JL;Shaw AT;Engelman JA
通讯作者：
Engelman JA
DOI：
10.1016/j.ypdi.2012.01.031
发表时间：
2012
期刊：
Yearbook of Pulmonary Disease
影响因子：
--
作者：
L. Tanoue
通讯作者：
L. Tanoue
影响因子：
2.7
作者：
Peilong Zhang;Jiaqiang Dong;B. Zhong;D. Zhang;C. Jin;Xuejing Meng;Desheng Sun;Xiangyuan Xu;Yong Zhou;Zhipeng Liang;Minghua Ji;Hailong Li;Tao Xu;Guowei Song;Ling Zhang;Gang-Ying Chen;Hongbin Yuan;J. Shih;Ruihao Zhang;Guojun Hou;Ying-ying Jin;Qiong Yang
通讯作者：
Peilong Zhang;Jiaqiang Dong;B. Zhong;D. Zhang;C. Jin;Xuejing Meng;Desheng Sun;Xiangyuan Xu;Yong Zhou;Zhipeng Liang;Minghua Ji;Hailong Li;Tao Xu;Guowei Song;Ling Zhang;Gang-Ying Chen;Hongbin Yuan;J. Shih;Ruihao Zhang;Guojun Hou;Ying-ying Jin;Qiong Yang
影响因子：
50.3
作者：
Zou HY;Friboulet L;Kodack DP;Engstrom LD;Li Q;West M;Tang RW;Wang H;Tsaparikos K;Wang J;Timofeevski S;Katayama R;Dinh DM;Lam H;Lam JL;Yamazaki S;Hu W;Patel B;Bezwada D;Frias RL;Lifshits E;Mahmood S;Gainor JF;Affolter T;Lappin PB;Gukasyan H;Lee N;Deng S;Jain RK;Johnson TW;Shaw AT;Fantin VR;Smeal T
通讯作者：
Smeal T
影响因子：
45.3
作者：
Gainor, Justin F.;Shaw, Alice T.
通讯作者：
Shaw, Alice T.