A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency
文献类型：期刊论文
| 作者 | Liu, C; Ding, HY; Li, XX; Pallasch, CP; Hong, LY; Guo, DW; Chen, Y; Wang, DF; Wang, W; Wang, YJ |
| 刊名 | EMBO MOLECULAR MEDICINE
 |
| 出版日期 | 2015 |
| 卷号 | 7期号:4页码:438-449 |
| 关键词 | DNA repair dual-targeting anticancer drug HDAC nitrogen mustard |
| 通讯作者 | Wang, YJ (reprint author), Second Mil Med Univ, Changhai Hosp, Dept Oncol, Shanghai, Peoples R China.,yajiewa0459@163.com ; hemann@mit.edu ; hai@sibcb.ac.cn |
| 英文摘要 | Genotoxic drugs constitute a major treatment modality for human cancers; however, cancer cells' intrinsic DNA repair capability often increases the threshold of lethality and renders these drugs ineffective. The emerging roles of HDACs in DNA repair provide new opportunities for improving traditional genotoxic drugs. Here, we report the development and characterization of CY190602, a novel bendamustine-derived drug with significantly enhanced anticancer potency. We show that CY190602's enhanced potency can be attributed to its newly gained ability to inhibit HDACs. Using this novel DNA/HDAC dual-targeting drug as a tool, we further explored HDAC's role in DNA repair. We found that HDAC activities are essential for the expression of several genes involved in DNA synthesis and repair, including TYMS, Tip60, CBP, EP300, and MSL1. Importantly, CY190602, the first-in-class example of such DNA/HDAC dual-targeting drugs, exhibited significantly enhanced anticancer activity invitro and invivo. These findings provide rationales for incorporating HDAC inhibitory moieties into genotoxic drugs, so as to overcome the repair capacity of cancer cells. Systematic development of similar DNA/HDAC dual-targeting drugs may represent a novel opportunity for improving cancer therapy. |
| 学科主题 | Research & Experimental Medicine |
| 类目[WOS] | Medicine, Research & Experimental |
| 关键词[WOS] | CHRONIC LYMPHOCYTIC-LEUKEMIA ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; DNA-DAMAGE RESPONSE ; DOUBLE-STRAND BREAKS ; FANCONI-ANEMIA ; CLINICAL-PRACTICE ; REPAIR PATHWAYS ; BENDAMUSTINE ; TUMOR ; ATM |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000352612400009 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/51]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Liu, C,Ding, HY,Li, XX,et al. A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency[J]. EMBO MOLECULAR MEDICINE,2015,7(4):438-449. |
| APA | Liu, C.,Ding, HY.,Li, XX.,Pallasch, CP.,Hong, LY.,...&Jiang, H.(2015).A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency.EMBO MOLECULAR MEDICINE,7(4),438-449. |
| MLA | Liu, C,et al."A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency".EMBO MOLECULAR MEDICINE 7.4(2015):438-449. |
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