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New strategies are needed, and could have an important impact on therapy. One approach could be to target other cellular mechanisms required for receptor activation. In prior work, we used a cell-based assay of AR conformation change to identify non-ligand inhibitors of AR activity. Here, we characterize 2 compounds identified in this screen: pyrvinium pamoate, a Food and Drug Administration-approved drug, and harmol hydrochloride, a natural product. Each compound functions by a unique, non-competitive mechanism and synergizes with competitive antagonists to disrupt AR activity. Harmol blocks DNA occupancy by AR, whereas pyrvinium does not. Pyrvinium inhibits AR-dependent gene expression in the prostate gland in vivo, and induces prostate atrophy. These results highlight new therapeutic strategies to inhibit AR activity.<\/jats:p>","DOI":"10.1073\/pnas.0807282106","type":"journal-article","created":{"date-parts":[[2009,4,10]],"date-time":"2009-04-10T20:58:32Z","timestamp":1239397112000},"page":"7233-7238","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["Non-competitive androgen receptor inhibition in vitro and in vivo"],"prefix":"10.1073","volume":"106","author":[{"given":"Jeremy O.","family":"Jones","sequence":"first","affiliation":[{"name":"Departments of Neurology,"},{"name":"Cellular and Molecular Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Bolton","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Biopharmaceutical Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementine","family":"Feau","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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