Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform
文献类型：期刊论文
| 作者 | Xie, Hua3 ; Lee, Mee-Hyun3; Zhu, Feng3; Reddy, Kanamata3; Peng, Cong3; Li, Yan3; Lim, Do Young3; Kim, Dong Joon3; Li, Xiang3; Kang, Soouk3
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| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2013-01-15 |
| 卷号 | 73期号:2页码:716-724 |
| ISSN号 | 0008-5472 |
| DOI | 10.1158/0008-5472.CAN-12-2784 |
| 文献子类 | Article |
| 英文摘要 | Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. In the present study, we used a ligand docking method to explore the novel scaffold of potential Aurora B inhibitors. One thousand compounds from our in-house compound library were screened against the Aurora B structure and one compound, (E)-3-((E)-4-(benzo[d][1,3] dioxol-5-yl)-2-oxobut-3-en-1-ylidene)indolin-2-one (designated herein as HOI-07) was selected for further study. HOI-07 potently inhibited in vitro Aurora B kinase activity in a dose-dependent manner, without obvious inhibition of another 49 kinases, including Aurora A. This compound suppressed Aurora B kinase activity in lung cancer cells, evidenced by the inhibition of the phosphorylation of histone H3 on Ser10 in a dose-and time-dependent manner. This inhibition resulted in apoptosis induction, G2-Marrest, polyploidy cells, and attenuation of cancer cell anchorage-independent growth. Moreover, knocking down the expression of Aurora B effectively reduced the sensitivity of cancer cells to HOI-07. Results of an in vivo xenograft mouse study showed that HOI-07 treatment effectively suppressed the growth of A549 xenografts, without affecting the body weight of mice. The expression of phospho-histone H3, phospho-Aurora B, and Ki-67 was also suppressed in the HOI-07 treatment group. Taken together, we identified HOI-07 as a specific Aurora B inhibitor, which deserves further investigation. Cancer Res; 73(2); 716-24. (C) 2012 AACR. |
| WOS关键词 | CANCER-CELLS ; DRUG TARGET ; A KINASE ; IN-VIVO ; OVEREXPRESSION ; CHECKPOINT ; ARREST ; POLES |
| 资助项目 | Hormel Foundation[00000000] ; NIH[R37 CA081064] ; NIH[CA120388] ; NIH[ES016548] ; NIH[CA0227501] ; National Cancer Institute[HHSN-261200533001C-NO1-CN-53301] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000313739500030 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277767]  |
| 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 | Dong, Zigang |
| 作者单位 | 1.NCI, Bethesda, MD 20892 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Beijing, Peoples R China 3.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA; |
| 推荐引用方式 GB/T 7714 | Xie, Hua,Lee, Mee-Hyun,Zhu, Feng,et al. Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform[J]. CANCER RESEARCH,2013,73(2):716-724. |
| APA | Xie, Hua.,Lee, Mee-Hyun.,Zhu, Feng.,Reddy, Kanamata.,Peng, Cong.,...&Dong, Zigang.(2013).Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform.CANCER RESEARCH,73(2),716-724. |
| MLA | Xie, Hua,et al."Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform".CANCER RESEARCH 73.2(2013):716-724. |
入库方式： OAI收割
来源：上海药物研究所
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