Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment

doi:10.1126/sciadv.aaz8031

	Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment
	Wang, Leiming 2; Cheng, Chiang-Min 2; Qin, Jun 3; Xu, Mafei 2; Kao, Chung-Yang 2; Shi, Jingjing 4; You, Erli 4; Gong, Wanchun 4; Rosa, Laura Pedro 5; Chase, Peter 5
刊名	SCIENCE ADVANCES
	2020-04-01
卷号	6 期号:18 页码:11
ISSN号	2375-2548
DOI	10.1126/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.
资助项目	NIH[DK071662] ; NIH[DK45641] ; NIH[HL114539] ; NIH National Institute of Mental Health[U54-MH084512]
WOS关键词	GROWTH ; IDENTIFICATION ; METASTASIS ; ROLES ; CELLS ; NURR1
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号	WOS:000531089700034
内容类型	期刊论文
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, Program Dev Biol, Houston, TX 77030 USA 2.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA 3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China 4.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 5.Mol Screening Ctr, Scripps Res, Jupiter, FL 33458 USA 6.Baylor Coll Med, Dept Med, Houston, TX 77030 USA 7.Discovery Technol, One Amgen Ctr Dr 29-1-B, Thousand Oaks, CA 91320 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.