Understanding the Cellular Pathways of Nuclear Receptor Activation

了解核受体激活的细胞途径

• 批准号: DP150102587
• 负责人: Prof Chris Porter
• 金额: $ 39.01万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2015
• 资助国家: 澳大利亚
• 起止时间: 2015-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP150102587
• 关键词: Understanding; Cellular; Pathways; Nuclear; Receptor

The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and to determine how the structure of these complexes dictates receptor activation. The data could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.

药物治疗的成功关键取决于特异性，即在目标部位刺激治疗反应，并避免在其他(可能有毒的)部位活动。该项目旨在探索药物如何与胞浆中的结合蛋白相互作用，诱导核受体的核运输和组织特异性激活--核受体是主要的药物靶点。该项目打算使用分子、结构和细胞生物学方法来绘制药物结合蛋白-受体相互作用图，并确定这些复合体的结构如何决定受体的激活。这些数据可以为设计与正确组织中的正确蛋白质相互作用的药物提供路线图，并在这样做的过程中显着提高药物的特异性。