B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest

doi:10.1007/s10637-008-9211-7

	B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest
	Xiong, Xishan 1; Zhang, Yingwei 3; Gao, Xiang 3; Dong, Zheyi 3; Li, Lin 3; Ji, Chengcheng 3; Fu, Lili 3; Luo, Xiaomin2 ; Liu, Hong2 ; Mei, Changlin 3
刊名	INVESTIGATIONAL NEW DRUGS
	2010-02
卷号	28 期号:1 页码:26-34
关键词	Pyrrole-substituted indolinone Cell cycle arrest Cyclin-dependent kinase Cdc2 Cyclin B1
ISSN号	0167-6997
DOI	10.1007/s10637-008-9211-7
文献子类	Article
英文摘要	(E)-Ethyl 3,5-dimethyl-4-[(indolin-2-one-3-ylidene)methyl]-1H-pyrrole-2-carboxylate (B5) was one of the novel pyrrole-substituted indolinones synthesized in our research with the initial aim of developing selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs). However, B5 exhibited weak inhibitory potency against a variety of protein tyrosine kinases including EGFR, but potent kinase inhibition against several members of the cyclin-dependent kinase (CDK) family. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that B5 had approximately 500 times more potent antitumor activity than PD153035, a known standard EGFR-TKI, in a panel of ten epithelial cancer cell lines. B5 did not inhibit the phosphorylation of EGFR induced by EGF in vitro. DNA flow cytometric analysis revealed that B5 induced cell cycle arrest at G2/M phase and western blot analysis indicated that both CDK1 (Cdc2) and cyclin B1 proteins were decreased after B5 treatment. Our findings suggested the potential therapeutic applications of B5 in numerous cancers and a promising new template for further development of antitumor agents.
资助项目	National 863 Plan in High Technology Progress[2002AA2Z3130] ; National 863 Plan in High Technology Progress[2007AA02Z3Z1] ; Shanghai Leading Academic Discipline Project[B902]
WOS关键词	GROWTH-FACTOR RECEPTOR ; GALLBLADDER ADENOCARCINOMA CELLS ; TYROSINE KINASE INHIBITORS ; DEPENDENT KINASES ; INDOLIN-2-ONE DERIVATIVES ; EPITHELIAL-CELLS ; ACTIVATION ; GEFITINIB ; CDK2 ; MECHANISM
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000273317700004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278982]
专题	药物化学研究室药物发现与设计中心
通讯作者	Mei, Changlin
作者单位	1.Acad Mil Med Sci, Dept Cardiol & Nephrol, Affiliated Hosp, Beijing 100071, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.Second Mil Med Univ, Changzheng Hosp, Nephrol Inst PLA, Div Nephrol, Shanghai 200003, Peoples R China;
推荐引用方式 GB/T 7714	Xiong, Xishan,Zhang, Yingwei,Gao, Xiang,et al. B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest[J]. INVESTIGATIONAL NEW DRUGS,2010,28(1):26-34.
APA	Xiong, Xishan.,Zhang, Yingwei.,Gao, Xiang.,Dong, Zheyi.,Li, Lin.,...&Mei, Changlin.(2010).B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest.INVESTIGATIONAL NEW DRUGS,28(1),26-34.
MLA	Xiong, Xishan,et al."B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest".INVESTIGATIONAL NEW DRUGS 28.1(2010):26-34.