[PDF][PDF] Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor
RJ Andersen, NR Mawji, J Wang, G Wang, S Haile… - Cancer cell, 2010 - cell.com
Cancer cell, 2010•cell.com
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 …
(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 …
Summary
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.
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