关键词：雄激素受体;雄激素;控制;功能;原因抑制剂;核医学;前列腺癌,前列腺;受体网站(生理学);感觉器官;目标
摘 要：The overall goal of this research project is to develop and implement a conceptually innovative strategy for extrinsic regulation of the androgen receptor (AR) to target the transcriptional misregulation mediated by this receptor in prostate cancer. This strategy utilizes bifunctional molecules that simultaneously interact with AR and with components of the chromatin remodeling machinery. In the second year of funding, a paper outlining the early stages of the study was accepted for publication. Additionally, thorough characterization of HDAC inhibitor-based structures revealed that localizing HDACs to promoters via AR leads is not efficacious. However, targeting an epigenetic reader, Brd4, lead to robust and reliable extrinsic control of full- length nuclear receptor function. In the final year of funding, this latter model will be fully extended in the prostate cancer system.