B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest
文献类型：期刊论文
| 作者 | Xiong, Xishan1; Zhang, Yingwei3; Gao, Xiang3; Dong, Zheyi3; Li, Lin3; Ji, Chengcheng3; Fu, Lili3; Luo, Xiaomin2 ; Liu, Hong2; Mei, Changlin3
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| 刊名 | INVESTIGATIONAL NEW DRUGS
 |
| 出版日期 | 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. |
| 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 |
| 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研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000273317700004 |
| 出版者 | SPRINGER |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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