Non-competitive androgen receptor inhibition in vitro and in vivo

Jeremy O. Jones, Eric C. Bolton, Yong Huang, Clementine Feau, R. Kiplin Guy, Keith R. Yamamoto, Byron Hann, Marc I. Diamond

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Androgen receptor (AR) inhibitors are used to treat multiple human diseases, including hirsutism, benign prostatic hypertrophy, and prostate cancer, but all available anti-androgens target only ligand binding, either by reduction of available hormone or by competitive antagonism. 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.

Original languageEnglish
Pages (from-to)7233-7238
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
StatePublished - Apr 28 2009


  • Antagonist
  • Harmol
  • Pyrvinium

ASJC Scopus subject areas

  • General


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