Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor

被引：428

作者：

Andersen, Raymond J. ^{[3
]}

Mawji, Nasrin R. ^{[1
]}

Wang, Jun ^{[1
]}

Wang, Gang ^{[1
]}

Haile, Simon ^{[1
]}

Myung, Jae-Kyung ^{[1
]}

Watt, Kate ^{[4
]}

Tam, Teresa ^{[1
]}

Yang, Yu Chi ^{[1
]}

Banuelos, Carmen A. ^{[1
]}

Williams, David E. ^{[2
]}

McEwan, Iain J. ^{[4
]}

Wang, Yuzhou ^{[2
]}

Sadar, Marianne D. ^{[1
]}

机构：

[1] British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[2] British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, Canada

[3] Univ British Columbia, Vancouver, BC V6T 1Z1, Canada

[4] Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, Scotland

来源：

CANCER CELL | 2010年 / 17卷 / 06期

关键词：

CREB-BINDING-PROTEIN; INDEPENDENT TRANSCRIPTIONAL ACTIVATION; SIGNAL-TRANSDUCTION PATHWAYS; NUCLEAR RECEPTORS; STEROID-BINDING; FACTORS INDUCE; BISPHENOL-A; CROSS-TALK; EXPRESSION; PROLIFERATION;

D O I：

10.1016/j.ccr.2010.04.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.

引用

页码：535 / 546

页数：12

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