典型文献
CHMFL-26 is a highly potent irreversible HER2 inhibitor for use in the treatment of HER2-positive and HER2-mutant cancers
文献摘要：
Oncogene HER2 is amplified in 20％-25％of human breast cancers and 6.1％-23.0％of gastric cancers,and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers.However,drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback.In this study,we discovered a potent irreversible HER2 kinase inhibitor,CHMFL-26,which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L,HER2 L755S,HER2 exon 20 insertions,and p95-HER2 truncation mutations.CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction.In addition,CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models.Together,these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.
文献关键词：
中图分类号：
作者姓名：
Jiang-yan Cao;Shuang Qi;Hong Wu;Ao-li Wang;Qing-wang Liu;Xi-xiang Li;Bei-lei Wang;Juan Ge;Feng-ming Zou;Cheng Chen;Jun-jie Wang;Chen Hu;Jing Liu;Wen-chao Wang;Qing-song Liu
作者机构：
Anhui Province Key Laboratory of Medical Physics and Technology,Institute of Health and Medical Technology,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230031,China;University of Science and Technology of China,Hefei 230026,China;Hefei Cancer Hospital,Chinese Academy of Sciences,Hefei 230031,China;Precision Medicine Research Laboratory of Anhui Province,Hefei 230088,China
文献出处：
引用格式：
[1]Jiang-yan Cao;Shuang Qi;Hong Wu;Ao-li Wang;Qing-wang Liu;Xi-xiang Li;Bei-lei Wang;Juan Ge;Feng-ming Zou;Cheng Chen;Jun-jie Wang;Chen Hu;Jing Liu;Wen-chao Wang;Qing-song Liu-.CHMFL-26 is a highly potent irreversible HER2 inhibitor for use in the treatment of HER2-positive and HER2-mutant cancers)[J].中国药理学报（英文版）,2022(10):2678-2686
A类：
CHMFL,V777L,L755S,p95,antiproliferation
B类：
highly,irreversible,HER2,inhibitor,treatment,positive,mutant,cancers,Oncogene,amplified,human,breast,gastric,directed,therapy,significantly,improves,outcome,patients,However,drug,resistance,still,clinical,challenge,due,primary,acquired,mutations,induced,negative,regulatory,feedback,In,this,study,discovered,kinase,which,covalently,targeted,cysteine,effectively,overcame,caused,by,exon,insertions,truncation,displayed,efficacy,against,cells,through,constant,mediated,signaling,pathway,inhibition,apoptosis,induction,addition,suppressed,tumor,growth,dose,dependent,manner,xenograft,mouse,models,Together,these,results,suggest,that,may,be,potential,novel,agent,overcoming
AB值：
0.531124
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
