Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer

Preethi Ravindranathan, Tae Kyung Lee, Lin Yang, Margaret M. Centenera, Lisa Butler, Wayne D. Tilley, Jer Tsong Hsieh, Jung Mo Ahn, Ganesh V. Raj

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


The growth of advanced prostate cancer depends on androgen receptor signalling, however treatment options are limited. Here we report the disruption of specific protein-protein interactions involving LXXLL motifs in androgen receptor-coregulator proteins such as PELP1 using a novel, small molecule peptidomimetic (D2). D2 is stable, non-toxic and efficiently taken up by prostate cancer cells. Importantly, D2 blocks androgen-induced nuclear uptake and genomic activity of the androgen receptor. Furthermore, D2 abrogates androgen-induced proliferation of prostate cancer cells in vitro with an IC 50 of 40 nM, and inhibits tumour growth in a mouse xenograft model. D2 also disrupts androgen receptor-coregulator interactions in ex vivo cultures of primary human prostate tumours. These findings provide evidence that targeting androgen receptor-coregulator interactions using peptidomimetics may be a viable therapeutic approach for patients with advanced prostate cancer.

Original languageEnglish (US)
Article number1923
JournalNature communications
StatePublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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