A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction
文献类型：期刊论文
| 作者 | Damaneh, Mohammadali Soleimani2,4; Hu, Jian-Ping3; Huan, Xia-Juan4; Song, Shan-Shan4; Tian, Chang-Qing2,4; Chen, Dan-Qi3 ; Meng, Tao3; Chen, Yue-Lei3; Shen, Jing-Kang3; Xiong, Bing3
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| 刊名 | INVESTIGATIONAL NEW DRUGS
 |
| 出版日期 | 2020-06-01 |
| 卷号 | 38期号:3页码:700-713 |
| 关键词 | BET inhibitor Cell proliferation Apoptosis Anti-cancer agent |
| ISSN号 | 0167-6997 |
| DOI | 10.1007/s10637-019-00818-z |
| 通讯作者 | Xiong, Bing(bxiong@simm.ac.cn) ; Miao, Ze-Hong(zhmiao@simm.ac.cn) ; Wang, Ying-Qing(yqwang@simm.ac.cn) |
| 英文摘要 | The bromodomain and extra-terminal domain (BET) family of proteins, especially bromodomain-containing protein 4 (BRD4), has emerged as exciting anti-tumor targets due to their important roles in epigenetic regulation. Therefore, the discovery of BET inhibitors with promising anti-tumor efficacy will provide a novel approach to epigenetic anticancer therapy. Recently, we discovered the new BET inhibitor compound 171, which is derived from a polo-like kinase 1 (PLK1)-BRD4 dual inhibitor based on our previous research. Compound 171 was found to maintain BET inhibition ability without PLK1 inhibition, and there was no selectivity among BET family members. The in vitro and in vivo results both indicated that the overall anti-tumor activity of compound 171 was improved compared with the (+)-JQ-1 or OTX-015 BET inhibitors. Furthermore, we found that compound 171 could regulate the expression of cell cycle-regulating proteins including c-Myc and p21 and induce cell cycle arrest in the G(0)/G(1) phase. However, compound 171 only has a quite limited effect on apoptosis, in considering that apoptosis was only observed at doses greater than 50 mu M. To determine the mechanisms underlying cell death, proliferation activity assay was conducted. The results showed that compound 171 induced clear anti-proliferative effects at doses that no obvious apoptosis was induced, which indicated that the cell cycle arresting effect contributed mostly to its anti-tumor activity. The result of this study revealed the anti-tumor mechanism of compound 171, and laid a foundation for the combination therapy in clinical practice, if compound 171 or its series compounds become drug candidates in the future. |
| WOS关键词 | PHASE-II TRIAL ; BROMODOMAIN PROTEIN ; BI 2536 ; DOSE-ESCALATION ; DRUG DISCOVERY ; OPEN-LABEL ; BRD4 ; CANCER ; OTX015 ; JQ1 |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000531213000013 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280195]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xiong, Bing; Miao, Ze-Hong; Wang, Ying-Qing |
| 作者单位 | 1.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Drugabil Res Marine Nat Prod, Shandong 266237, Peoples R China 2.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Damaneh, Mohammadali Soleimani,Hu, Jian-Ping,Huan, Xia-Juan,et al. A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction[J]. INVESTIGATIONAL NEW DRUGS,2020,38(3):700-713. |
| APA | Damaneh, Mohammadali Soleimani.,Hu, Jian-Ping.,Huan, Xia-Juan.,Song, Shan-Shan.,Tian, Chang-Qing.,...&Wang, Ying-Qing.(2020).A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction.INVESTIGATIONAL NEW DRUGS,38(3),700-713. |
| MLA | Damaneh, Mohammadali Soleimani,et al."A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction".INVESTIGATIONAL NEW DRUGS 38.3(2020):700-713. |
入库方式： OAI收割
来源：上海药物研究所
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