Design and optimize N-substituted EF24 as effective and low toxicity NF-kappa B inhibitor for lung cancer therapy via apoptosis-to-pyroptosis switch

doi:10.1111/cbdd.13514

科研成果详情

题名	Design and optimize N-substituted EF24 as effective and low toxicity NF-kappa B inhibitor for lung cancer therapy via apoptosis-to-pyroptosis switch
作者	Chen, Liping 1; Li, Qian 1; Zheng, Zhiwei1; Xie, Jingwen 1; Lin, Xiaoming 2; Jiang, Chengxi 1; Xu, Haineng 1; Wu, Xiaoping1,3; Wu, Jianzhang1; Zhang, Huajie1
发表期刊	CHEMICAL BIOLOGY & DRUG DESIGN 影响因子和分区
语种	英语
原始文献类型	Article
关键词	anti-lung cancer apoptosis NF-kappa B inhibitor pyroptosis toxicity
其他关键词	QUALITY-OF-LIFE ; CHEMOTHERAPY ; PATHWAYS ; CELLS ; ANTITUMOR ; PROTEINS
摘要	As NF-kappa B signaling pathway is constitutively activated in lung cancer, targeting NF-kappa B has a potential for the treatment. EF24 has been proved to be a NF-kappa B inhibitor with good antitumor activity, while whose toxicity possibly became one of the obstacles to enter into clinical application. In order to find high efficiency and low toxicity NF-kappa B inhibitors, EF24 was modified and 13d was screened out. It was proved that 13d possessed an effective combination of inhibiting NF-kappa B pathway and showing lower cytotoxicity on normal cells as well as less toxicity in acute toxicity experiment compared with the lead compound of EF24. In addition, 13d was found to inhibit cell vitality, arrest cell cycle in G2/M phase, promote cell apoptosis, and suppress the xenograft tumor growth. Furthermore, 13d was elucidated to induce pyroptosis developing from apoptosis, which was associated with the inhibition of NF-kappa B. Taken together, it was suggested that 13d was a potent antitumor agent.
资助项目	ZheJiang Province Natural Science Fund of China [LY15H160062, LY15H280014, LY17H160059]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81703766]; Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences; General Scientific Research Projects of Zhejiang Education Department [Y201839895]
出版者	WILEY
出版地	HOBOKEN
ISSN	1747-0277
EISSN	1747-0285
卷号	94 期号:1 页码:1368-1377
DOI	10.1111/cbdd.13514
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
WOS记录号	WOS:000477020400009
收录类别	SCIE ; PUBMED ; SCOPUS
发表日期	2019-07
URL	查看原文
Pubmed记录号	30873716
Scopus记录号	2-s2.0-85064712566
引用统计	被引频次：13[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/5459
专题	药学院（分析测试中心）
通讯作者	Wu, Jianzhang; Zhang, Huajie
作者单位	1.Wenzhou Med Univ, Coll Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou, Zhejiang, Peoples R China; 2.Whenzhou Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Wenzhou, Zhejiang, Peoples R China; 3.Jinan Univ, Inst Tissue Transplantat & Immunol, Guangzhou, Guangdong, Peoples R China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）; 药学院（分析测试中心）; 药学院（分析测试中心）
推荐引用方式 GB/T 7714	Chen, Liping,Li, Qian,Zheng, Zhiwei,et al. Design and optimize N-substituted EF24 as effective and low toxicity NF-kappa B inhibitor for lung cancer therapy via apoptosis-to-pyroptosis switch[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2019,94(1):1368-1377.
APA	Chen, Liping., Li, Qian., Zheng, Zhiwei., Xie, Jingwen., Lin, Xiaoming., ... & Zhang, Huajie. (2019). Design and optimize N-substituted EF24 as effective and low toxicity NF-kappa B inhibitor for lung cancer therapy via apoptosis-to-pyroptosis switch. CHEMICAL BIOLOGY & DRUG DESIGN, 94(1), 1368-1377.
MLA	Chen, Liping,et al."Design and optimize N-substituted EF24 as effective and low toxicity NF-kappa B inhibitor for lung cancer therapy via apoptosis-to-pyroptosis switch".CHEMICAL BIOLOGY & DRUG DESIGN 94.1(2019):1368-1377.