Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/78419
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Type: Journal article
Title: Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer
Author: Ravindranathan, P.
Lee, T.
Yang, L.
Centenera, M.
Butler, L.
Tilley, W.
Hsieh, J.
Ahn, J.
Raj, G.
Citation: Nature Communications, 2013; 4(5):1923-1-1923-11
Publisher: Nature Publishing Group
Issue Date: 2013
ISSN: 2041-1723
2041-1723
Statement of
Responsibility: 
Preethi Ravindranathan, Tae-Kyung Lee, Lin Yang, Margaret M. Centenera, Lisa Butler, Wayne D. Tilley, Jer-Tsong Hsieh, Jung-Mo Ahn and Ganesh V. Raj
Abstract: 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 IC50 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.
Keywords: Cell Line, Tumor; Cell Nucleus; Animals; Humans; Mice; Prostatic Neoplasms; Receptors, Androgen; Transcription Factors; Microscopy, Fluorescence; Prostatectomy; Xenograft Model Antitumor Assays; Cell Proliferation; Transcription, Genetic; Amino Acid Motifs; Protein Structure, Tertiary; Protein Binding; Protein Transport; Models, Molecular; Male; Co-Repressor Proteins; Peptidomimetics
Description: Extent: 11 p.
Rights: © 2013 Macmillan Publishers Limited. All rights reserved.
RMID: 0020128666
DOI: 10.1038/ncomms2912
Grant ID: http://purl.org/au-research/grants/nhmrc/627185
Appears in Collections:Medicine publications

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