Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer
文献类型：期刊论文
| 作者 | Xiang, Quping1,2; Zhang, Yan1,2; Li, Jiaguo2,3; Xue, Xiaoqian1,2; Wang, Chao2; Song, Ming2; Zhang, Cheng2,3; Wang, Rui2; Li, Chenchang2,3; Wu, Chun2 |
| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2018-03-01 |
| 卷号 | 9期号:3页码:262-267 |
| 关键词 | Bromodomain Brd4 Prostate Cancer Epigenetics |
| ISSN号 | 1948-5875 |
| DOI | 10.1021/acsmedchemlett.8b00003 |
| 文献子类 | Article |
| 英文摘要 | Prostate cancer is a commonly diagnosed cancer and a leading cause of cancer-related deaths. The bromodomain and extra terminal domain (BET) family proteins have emerged as potential therapeutic targets for the treatment of castration resistant prostate cancer. A series of 2,2-dimethy1-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC50 values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds 36 (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In in vivo studies, 36 demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development. |
| WOS关键词 | INCREASED SURVIVAL ; BROMODOMAINS ; OPTIMIZATION ; ABIRATERONE ; CASTRATION ; STATISTICS ; RESISTANCE ; DISCOVERY |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000427331200017 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/168890]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Xu, Yong |
| 作者单位 | 1.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China 2.Guangzhou Med Univ, Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Joint Sch Life Sci,Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China 3.Jilin Univ, Sch Pharmaceut Sci, 1266 Fujin Rd, Changchun 130021, Jilin, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Liaoning, Peoples R China 5.Jinan Univ, Sch Pharm, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiang, Quping,Zhang, Yan,Li, Jiaguo,et al. Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer[J]. ACS MEDICINAL CHEMISTRY LETTERS,2018,9(3):262-267. |
| APA | Xiang, Quping.,Zhang, Yan.,Li, Jiaguo.,Xue, Xiaoqian.,Wang, Chao.,...&Xu, Yong.(2018).Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer.ACS MEDICINAL CHEMISTRY LETTERS,9(3),262-267. |
| MLA | Xiang, Quping,et al."Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer".ACS MEDICINAL CHEMISTRY LETTERS 9.3(2018):262-267. |
入库方式： OAI收割
来源：大连化学物理研究所
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