Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer

doi:10.1021/acsmedchemlett.8b00003

	Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer
	Xiang, Quping 1,2; Zhang, Yan 1,2; Li, Jiaguo 2,3; Xue, Xiaoqian 1,2; Wang, Chao 2; Song, Ming 2; Zhang, Cheng 2,3; Wang, Rui 2; Li, Chenchang 2,3; Wu, Chun 2
刊名	ACS MEDICINAL CHEMISTRY LETTERS
	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
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000427331200017
内容类型	期刊论文
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.