Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor

Raymond J. Andersen; Nasrin R. Mawji; Jun Wang; Gang Wang; Simon Haile; Jae-Kyung Myung; Kate Watt; Teresa Tam; Yu Chi Yang; Carmen A. Bañuelos; David E. Williams; Iain J. McEwan; Yuzhou Wang; Marianne D. Sadar

doi:10.1016/j.ccr.2010.04.027

Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor

Raymond J. Andersen, Nasrin R. Mawji, Jun Wang, Gang Wang, Simon Haile, Jae-Kyung Myung, Kate Watt, Teresa Tam, Yu Chi Yang, Carmen A. Bañuelos, David E. Williams, Iain J. McEwan, Yuzhou Wang, Marianne D. Sadar

Medical Sciences

Research output: Contribution to journal › Article › peer-review

423 Citations (Scopus)

Abstract

Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.

Original language	English
Pages (from-to)	535-546
Number of pages	12
Journal	Cancer Cell
Volume	17
Issue number	6
Early online date	14 Jun 2010
DOIs	https://doi.org/10.1016/j.ccr.2010.04.027
Publication status	Published - 15 Jun 2010

Keywords

cellcycle

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ccr.2010.04.027

Cite this

Andersen, R. J., Mawji, N. R., Wang, J., Wang, G., Haile, S., Myung, J.-K., Watt, K., Tam, T., Yang, Y. C., Bañuelos, C. A., Williams, D. E., McEwan, I. J., Wang, Y., & Sadar, M. D. (2010). Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell, 17(6), 535-546. https://doi.org/10.1016/j.ccr.2010.04.027

Andersen, RJ, Mawji, NR, Wang, J, Wang, G, Haile, S, Myung, J-K, Watt, K, Tam, T, Yang, YC, Bañuelos, CA, Williams, DE, McEwan, IJ, Wang, Y & Sadar, MD 2010, 'Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor', Cancer Cell, vol. 17, no. 6, pp. 535-546. https://doi.org/10.1016/j.ccr.2010.04.027

@article{b7509b3d59f0468da03d0df58f3a1fe8,

title = "Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor",

abstract = "Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.",

keywords = "cellcycle",

author = "Andersen, {Raymond J.} and Mawji, {Nasrin R.} and Jun Wang and Gang Wang and Simon Haile and Jae-Kyung Myung and Kate Watt and Teresa Tam and Yang, {Yu Chi} and Ba{\~n}uelos, {Carmen A.} and Williams, {David E.} and McEwan, {Iain J.} and Yuzhou Wang and Sadar, {Marianne D.}",

year = "2010",

month = jun,

day = "15",

doi = "10.1016/j.ccr.2010.04.027",

language = "English",

volume = "17",

pages = "535--546",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor

AU - Andersen, Raymond J.

AU - Mawji, Nasrin R.

AU - Wang, Jun

AU - Wang, Gang

AU - Haile, Simon

AU - Myung, Jae-Kyung

AU - Watt, Kate

AU - Tam, Teresa

AU - Yang, Yu Chi

AU - Bañuelos, Carmen A.

AU - Williams, David E.

AU - McEwan, Iain J.

AU - Wang, Yuzhou

AU - Sadar, Marianne D.

PY - 2010/6/15

Y1 - 2010/6/15

N2 - Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.

AB - Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.

KW - cellcycle

U2 - 10.1016/j.ccr.2010.04.027

DO - 10.1016/j.ccr.2010.04.027

M3 - Article

SN - 1535-6108

VL - 17

SP - 535

EP - 546

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this