Author/Authors :
Andersen، نويسنده , , Raymond J. and Mawji، نويسنده , , Nasrin R. and Wang، نويسنده , , Jun and Wang، نويسنده , , Gang and Haile، نويسنده , , Simon and Myung، نويسنده , , Jae-Kyung and Watt، نويسنده , , Kate and Tam، نويسنده , , Teresa and Yang، نويسنده , , Yu Chi and Baٌuelos، نويسنده , , Carmen A. and Williams، نويسنده , , David E. and McEwan، نويسنده , , Iain J. and Wang، نويسنده , , Yuzhou and Sadar، نويسنده , , Marianne D.، نويسنده ,
Abstract :
Summary
tion-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.
