A cellular conformation-based screen for androgen receptor inhibitors

Jeremy O. Jones, Marc I. Diamond

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The androgen receptor (AR), a member of the steroid nuclear receptor family of transcription factors, regulates a wide range of physiological processes. Androgen signaling is also associated with numerous human diseases, including prostate cancer. All current anti-androgen therapies reduce ligand access to AR, whether by competitive antagonism or inhibition of androgen production, but are limited by acquired resistance and serious side-effects. Thus, novel antiandrogens that target events subsequent to ligand binding could have important therapeutic value. We developed a high throughput assay that exploits fluorescence resonance energy transfer (FRET) to measure ligand-induced conformation change in AR. We directly compared this assay to a transcription-based assay in a screen of FDA-approved compounds and natural products. The FRET-based screen identified compounds with previously unrecognized antiandrogen activities, with equivalent sensitivity and superior specificity compared to a reporter-based screen. This approach can thus improve the identification of small molecule AR inhibitors.

Original languageEnglish (US)
Pages (from-to)412-418
Number of pages7
JournalACS chemical biology
Issue number7
StatePublished - Jul 18 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine


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