MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubules
文献类型：期刊论文
| 作者 | Zhang, Zhixiang1; Meng, Tao2 ; He, Jingxue1; Li, Ming1; Tong, Lin-Jiang1; Xiong, Bing2; Lin, Liping1; Shen, Jingkang2; Miao, Ze-Hong1; Ding, Jian1
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| 刊名 | INVESTIGATIONAL NEW DRUGS
 |
| 出版日期 | 2010-12 |
| 卷号 | 28期号:6页码:715-728 |
| 关键词 | Mitosis Tubulin Anticancer drug cDNA microarray Connectivity Map |
| ISSN号 | 0167-6997 |
| DOI | 10.1007/s10637-009-9303-z |
| 文献子类 | Article |
| 英文摘要 | Targeting cellular mitosis is an attractive antitumor strategy. Here, we reported MT7, a novel compound from the 6H-Pyrido[2',1':2,3]imidazo [4,5-c]isoquinolin- 5(6H)-one library generated by using the multi-component reaction strategy, as a new mitotic inhibitor. MT7 elicited apparent inhibition of cell proliferation by arresting mitosis specifically and reversibly in various tumor cell lines originating from different human tissues. Detailed mechanistic studies revealed that MT7 induced typical gene expression profiles related to mitotic arrest shown by cDNA microarray assays. Connectivity Map was used to analyze the microarray data and suggested that MT7 was possibly a tubulin inhibitor due to its similar gene expression profiles to those of the known tubulin inhibitors demecolcine, celastrol and paclitaxel. Further analyses demonstrated that MT7 inhibited the polymerization of cellular microtubules although it was not detectable to bind to purified tubulin. The inhibition of cellular tubulin polymerization by MT7 subsequently resulted in the disruption of mitotic spindle formation, activated the spindle assembly checkpoint and consequently arrested the cells at mitosis. The persistent mitotic arrest by the treatment with MT7 led the tested tumor cells to apoptosis. Our data indicate that MT7 could act as a promising lead for further optimization, in hopes of developing new anticancer therapeutics and being used to probe the biology of mitosis, specifically, the mode of interference with microtubules. |
| WOS关键词 | SPINDLE-ASSEMBLY CHECKPOINT ; HUMAN CELL-CYCLE ; MITOTIC REPRESSION ; IN-VIVO ; TOPOISOMERASE-II ; TRANSCRIPTION ELONGATION ; CONNECTIVITY MAP ; DNA CLEAVAGE ; TUBULIN ; KINASE |
| 资助项目 | National Natural Science Foundation of China (NSFC)[30873092] ; National Natural Science Foundation of China (NSFC)[30721005] ; Science and Technology Commission of Shanghai Municipality (STCSM)[08PJ14113] ; Science and Technology Commission of Shanghai Municipality (STCSM)[08DZ1980200] |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000283097600001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278707]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Miao, Ze-Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Med Chem, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Zhixiang,Meng, Tao,He, Jingxue,et al. MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubules[J]. INVESTIGATIONAL NEW DRUGS,2010,28(6):715-728. |
| APA | Zhang, Zhixiang.,Meng, Tao.,He, Jingxue.,Li, Ming.,Tong, Lin-Jiang.,...&Ding, Jian.(2010).MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubules.INVESTIGATIONAL NEW DRUGS,28(6),715-728. |
| MLA | Zhang, Zhixiang,et al."MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubules".INVESTIGATIONAL NEW DRUGS 28.6(2010):715-728. |
入库方式： OAI收割
来源：上海药物研究所
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