.

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

TitleRegression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor
Publication TypeJournal Article
Year of Publication2010
AuthorsAndersen RJ, Mawji NR, Wang J, Wang G, Haile S, Myung J-, Watt K, Tam T, Yang YC, Banuelos CA, Williams DE, McEwan IJ, Wang Y, Sadar MD
JournalCancer cell
Volume17
Issue6
Pagination535 - 46
Date Published2010///
ISBN Number1878-3686
Abstract

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.[on SciFinder (R)]


a place of mind, The University of British Columbia

Department of Chemistry
2036 Main Mall
Vancouver, BC Canada V6T 1Z1
Tel: 604.822.3266
Fax: 604.822.2847

Emergency Procedures | Accessibility | Contact UBC | © Copyright The University of British Columbia