Article ID Journal Published Year Pages File Type
2107753 Cancer Cell 2010 12 Pages PDF
Abstract

SummaryCastration-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.

► Identified a specific small molecular inhibitor of AR N-terminal domain (NTD) ► This compound reduced protein-protein interactions with the NTD ► This compound inhibited constitutively active AR lacking ligand-binding domain ► This inhibitor caused cytoreduction of castrate-recurrent prostate cancer

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