Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor

Raymond J. Andersen, Nasrin R. Mawji, Jun Wang, Gang Wang, Simon Haile, Jae-Kyung Myung, Kate Watt, Teresa Tam, Yu Chi Yang, Carmen A. Bañuelos, David E. Williams, Iain J. McEwan, Yuzhou Wang, Marianne D. Sadar

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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.
Original languageEnglish
Pages (from-to)535-546
Number of pages12
JournalCancer Cell
Issue number6
Early online date14 Jun 2010
Publication statusPublished - 15 Jun 2010



  • cellcycle

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