A novel phosphoramide compound, DCZ0847, displays in vitro and in vivo anti-myeloma activity, alone or in combination with bortezomib
文献类型：期刊论文
| 作者 | Chen, Gege2; Hu, Ke2,4; Sun, Haiguo3; Zhou, Jinfeng2; Song, Dongliang2; Xu, Zhijian3 ; Gao, Lu2; Lu, Ye5; Cheng, Yao2; Feng, Qilin2
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| 刊名 | CANCER LETTERS
 |
| 出版日期 | 2020-05-28 |
| 卷号 | 478页码:45-55 |
| 关键词 | Multiple myeloma Bone marrow microenvironment DNA damage JAK2/STAT3 pathway |
| ISSN号 | 0304-3835 |
| DOI | 10.1016/j.canlet.2020.03.006 |
| 通讯作者 | Li, Bo(boli@simm.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn) |
| 英文摘要 | Multiple myeloma (MM) is an incurable hematological malignancy, for which novel effective therapies are urgently needed. We synthesized a novel phosphoramide compound, DCZ0847, showing a potent anti-myeloma activity both in vitro and in vivo. DCZ0847 showed high cytotoxicity towards primary MM cells but had no effect on normal cells and was well tolerated in vivo. The anti-myeloma activity of DCZ0847 was associated with inhibition of cell proliferation; promotion of cell apoptosis via mitochondrial transmembrane potential collapse and caspase-mediated extrinsic or intrinsic apoptotic pathways; and the induction of G2/M phase arrest via downregulation of CDC25C, CDK1, and cyclin B1. In particular, DCZ0847 induced DNA damage and triggered a DNA-damage response by enhancing the levels of gamma-H2A.X, phosphorylated (p)-ATM, p-ATR, p-Chk1, and p-Chk2. Additionally, DCZ0847 was able to overcome the bone marrow stromal cells-induced proliferation of MM cells and blocked JAK2/STAT3 signaling. Importantly, DCZ0847 acted synergistically with bortezomib, with the combination exerting greater cytotoxic effects in vitro and in vivo. Together, our results indicate that DCZ0847, alone or in combination with bortezomib, may represent a potential new therapy for patients with MM. |
| WOS关键词 | DRUG-RESISTANCE ; LENALIDOMIDE ; MICROENVIRONMENT ; DEXAMETHASONE ; INHIBITOR ; PATHWAY |
| 资助项目 | National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81870158] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000525868400005 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280030]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Bo; Zhu, Weiliang; Shi, Jumei |
| 作者单位 | 1.Nantong Univ, Med Sch, 19 Qixiu Rd, Nantong 226001, Peoples R China 2.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, 301 Yanchang Rd, Shanghai 200072, Peoples R China 3.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Nanjing Med Univ, Sch Clin Med, Nanjing 210000, Peoples R China 5.Soochow Univ, Dept Hematol & Oncol, Affiliated Taicang Hosp, Peoples Hosp Taicang 1, Suzhou 215400, Jiangsu, Peoples R China 6.Tongji Univ, Canc Ctr, Shanghai 200092, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Gege,Hu, Ke,Sun, Haiguo,et al. A novel phosphoramide compound, DCZ0847, displays in vitro and in vivo anti-myeloma activity, alone or in combination with bortezomib[J]. CANCER LETTERS,2020,478:45-55. |
| APA | Chen, Gege.,Hu, Ke.,Sun, Haiguo.,Zhou, Jinfeng.,Song, Dongliang.,...&Shi, Jumei.(2020).A novel phosphoramide compound, DCZ0847, displays in vitro and in vivo anti-myeloma activity, alone or in combination with bortezomib.CANCER LETTERS,478,45-55. |
| MLA | Chen, Gege,et al."A novel phosphoramide compound, DCZ0847, displays in vitro and in vivo anti-myeloma activity, alone or in combination with bortezomib".CANCER LETTERS 478(2020):45-55. |
入库方式： OAI收割
来源：上海药物研究所
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