Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor.
Cancer Cell
; 17(6): 535-46, 2010 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-20541699
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.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Compostos Benzidrílicos
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Castração
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Cloridrinas
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Antineoplásicos Hormonais
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Antagonistas de Receptores de Andrógenos
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Recidiva Local de Neoplasia
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article