典型文献
cyy-287,a novel pyrimidine-2,4-diamine derivative,inhibits tumor growth of EGFR-driven non-small cell lung cancer via the ERK pathway
文献摘要：
In recent decades,EGFR-targeted tyrosine kinase inhibitors(TKIs)have been proven to be an effective therapy for EGFR-mutant non-small cell lung cancer(NSCLC).However,resistance to EGFR-TKIs limits their clinical application.In the present study,we investigate the antitumor effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative,cyy-287,in NSCLC.We find that cyy-287 has a high affinity for lung tissue and inhibits the proliferation of NSCLC cells.Interestingly,the significant suppression of migration and induction of apoptosis by cyy-287 are only observed in EGFR-driven but not in EGFR-wild-type(wt)cells.According to the RNA sequencing and KEGG enrichment analysis results,cyy-287 markedly inhibits the MAPK pathway in EGFR-driven PC9 cells,and western blot analysis results further indicate that cyy-287 selectively blocks the ERK pathway in EGFR-driven cells.Meanwhile,apoptosis induced by cyy-287 could be partially reversed by ERK pathway inhibition.Further experi-ment indicates that cyy-287 inhibits the EGFR pathway in both EGFR-driven and EGFR-overexpressing cells.In-terestingly,it only induces apoptosis in EGFR-driven cells,not in EGFR-overexpressing cells.The growth of EGFR-driven cells is suppressed by cyy-287 in vivo,with fewer side effects.Our results suggest that cyy-287 may be a potential therapeutic drug with promising antitumor effects against NSCLC.
文献关键词：
中图分类号：
作者姓名：
Qianwen Zhang;Huijing Huang;Shuwen Zheng;Yelin Tang;Xiaodan Zhang;Qianqian Zhu;Zefeng Ni;Xiaohui Zheng;Kun Wang;Lehao Huang;Yunjie Zhao;Zhiguo Liu;Jianchang Qian
作者机构：
Institute of Molecular Toxicology and Pharmacology,Wenzhou Medical University,Wenzhou 325035,China;Chemical Biology Research Center at School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China
文献出处：
引用格式：
[1]Qianwen Zhang;Huijing Huang;Shuwen Zheng;Yelin Tang;Xiaodan Zhang;Qianqian Zhu;Zefeng Ni;Xiaohui Zheng;Kun Wang;Lehao Huang;Yunjie Zhao;Zhiguo Liu;Jianchang Qian-.cyy-287,a novel pyrimidine-2,4-diamine derivative,inhibits tumor growth of EGFR-driven non-small cell lung cancer via the ERK pathway)[J].生物化学与生物物理学报（英文版）,2022(10):1540-1551
A类：
cyy
B类：
novel,pyrimidine,diamine,derivative,inhibits,growth,EGFR,driven,small,lung,cancer,via,ERK,pathway,recent,decades,targeted,tyrosine,kinase,inhibitors,TKIs,have,been,proven,effective,therapy,mutant,NSCLC,However,resistance,limits,their,clinical,application,present,study,investigate,antitumor,underlying,mechanism,We,find,that,has,high,affinity,tissue,proliferation,cells,Interestingly,significant,suppression,migration,induction,apoptosis,by,are,only,observed,but,not,wild,type,According,sequencing,enrichment,analysis,results,markedly,MAPK,PC9,western,blot,further,selectively,blocks,Meanwhile,induced,could,partially,reversed,inhibition,Further,experi,indicates,both,overexpressing,induces,suppressed,vivo,fewer,side,effects,Our,suggest,may,potential,therapeutic,drug,promising,against
AB值：
0.462425
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