中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment

文献类型：期刊论文

作者Wang, Leiming3; Cheng, Chiang-Min3; Qin, Jun4; Xu, Mafei3; Kao, Chung-Yang3; Shi, Jingjing5; You, Erli5; Gong, Wanchun5; Rosa, Laura Pedro6; Chase, Peter6
刊名SCIENCE ADVANCES
出版日期2020-04-01
卷号6期号:18页码:11
ISSN号2375-2548
DOI10.1126/sciadv.aaz8031
通讯作者Tsai, Sophia Y.(stsai@bcm.edu) ; Tsai, Ming-Jer(mtsai@bcm.edu)
英文摘要The orphan nuclear receptor COUP-TFII is expressed at a low level in adult tissues, but its expression is increased and shown to promote progression of multiple diseases, including prostate cancer, heart failure, and muscular dystrophy. Suppression of COUP-TFII slows disease progression, making it an intriguing therapeutic target. Here, we identified a potent and specific COUP-TFII inhibitor through high-throughput screening. The inhibitor specifically suppressed COUP-TFII activity to regulate its target genes. Mechanistically, the inhibitor directly bound to the COUP-TFII ligand-binding domain and disrupted COUP-TFII interaction with transcription regulators, including FOXA1, thus repressing COUP-TFII activity on target gene regulation. Through blocking COUP-TFII's oncogenic activity in prostate cancer, the inhibitor efficiently exerted a potent antitumor effect in xenograft mouse models and patient-derived xenograft models. Our study identified a potent and specific COUP-TFII inhibitor that may be useful for the treatment of prostate cancer and possibly other diseases.
WOS关键词GROWTH ; IDENTIFICATION ; METASTASIS ; ROLES ; CELLS ; NURR1
资助项目NIH[DK071662] ; NIH[DK45641] ; NIH[HL114539] ; NIH National Institute of Mental Health[U54-MH084512]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000531089700034
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/280164]  
专题中国科学院上海药物研究所
通讯作者Tsai, Sophia Y.; Tsai, Ming-Jer
作者单位1.Baylor Coll Med, Dept Med, Houston, TX 77030 USA
2.Discovery Technol, One Amgen Ctr Dr 29-1-B, Thousand Oaks, CA 91320 USA
3.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
4.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct & Funct Drug Targets, VARI SIMM Ctr,CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
6.Mol Screening Ctr, Scripps Res, Jupiter, FL 33458 USA
7.Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA
推荐引用方式
GB/T 7714		 Wang, Leiming,Cheng, Chiang-Min,Qin, Jun,et al. Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment[J]. SCIENCE ADVANCES,2020,6(18):11.
APA Wang, Leiming.,Cheng, Chiang-Min.,Qin, Jun.,Xu, Mafei.,Kao, Chung-Yang.,...&Tsai, Ming-Jer.(2020).Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment.SCIENCE ADVANCES,6(18),11.
MLA Wang, Leiming,et al."Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment".SCIENCE ADVANCES 6.18(2020):11.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。