Discovery of novel inhibitors targeting the menin-mixed lineage leukemia interface using pharmacophore- and docking-based virtual screening
文献类型：期刊论文
| 作者 | Xu, Yuan1,2; Yue, Liyan1,2; Wang, Yulan1,2; Xing, Jin1,2; Chen, Zhifeng4; Shi, Zhe3; Liu, Rongfeng3; Liu, Yu-Chih3; Luo, Xiaomin1; Jiang, Hualiang1,4 |
| 刊名 | Journal of chemical information and modeling
 |
| 出版日期 | 2016-09-01 |
| 卷号 | 56期号:9页码:1847-1855 |
| ISSN号 | 1549-9596 |
| DOI | 10.1021/acs.jcim.6b00185 |
| 通讯作者 | Luo, cheng(cluo@simm.ac.cn) ; Zheng, mingyue(myzheng@simm.ac.cn) |
| 英文摘要 | Disrupting the interaction between mixed lineage leukemia (mll) fusion protein and menin provides a therapeutic approach for mll-mediated leukemia. here, we aim to discover novel inhibitors targeting the menin-mll interface with virtual screening. both structure-based molecular docking and ligand-based pharmacophore models were established, and the models used for compound screening show a remarkable ability to retrieve known active ligands from decoy molecules. verified by a fluorescence polarization assay, five hits with novel scaffolds were identified. among them, dcz_m123 exhibited potent inhibitory activity with an ic50 of 4.71 +/- 0.12 mu m and a k-d of 14.70 +/- 2.13 mu m, and it can effectively inhibit the human mll-rearranged leukemia cells mv4;11 and kopn8 with gi(50) values of 0.84 mu m and 0.54 mu m, respectively. |
| WOS关键词 | MLL-FUSION PROTEINS ; TRANSFORMATION ; LEUKEMOGENESIS ; BLOCK ; GENE |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry ; Computer Science |
| WOS类目 | Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Computer Science, Information Systems ; Computer Science, Interdisciplinary Applications |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000384271400022 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375034 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Luo, Cheng; Zheng, Mingyue |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Shanghai ChemPartner LifeSci Co Ltd, 5 Bldg,998 Halei Rd, Shanghai 201203, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Yuan,Yue, Liyan,Wang, Yulan,et al. Discovery of novel inhibitors targeting the menin-mixed lineage leukemia interface using pharmacophore- and docking-based virtual screening[J]. Journal of chemical information and modeling,2016,56(9):1847-1855. |
| APA | Xu, Yuan.,Yue, Liyan.,Wang, Yulan.,Xing, Jin.,Chen, Zhifeng.,...&Zheng, Mingyue.(2016).Discovery of novel inhibitors targeting the menin-mixed lineage leukemia interface using pharmacophore- and docking-based virtual screening.Journal of chemical information and modeling,56(9),1847-1855. |
| MLA | Xu, Yuan,et al."Discovery of novel inhibitors targeting the menin-mixed lineage leukemia interface using pharmacophore- and docking-based virtual screening".Journal of chemical information and modeling 56.9(2016):1847-1855. |
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来源：中国科学院大学
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