STRUCTURE OF HUMAN MEMBRANE CYTOCHROME P450 INVOLVED IN ANDROGEN BIOSYNTHESIS

参与雄激素生物合成的人膜细胞色素P450的结构

• 批准号: 8362388
• 负责人: Emily E Scott
• 金额: $ 0.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362388
• 关键词: Anabolism; Androgens; Clinical Trials; Complex; Cytochrome P450; Drug Design; Enzymes; Estrogens; Funding; Grant; Human; Malignant neoplasm of prostate; Membrane; National Center for Research Resources; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Source; Structure; United States National Institutes of Health; base; cancer therapy; cost; design; improved; inhibitor/antagonist; malignant breast neoplasm; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There are currently no structures of this important enzyme involved in androgen (and estrogen) synthesis. 80% of prostate cancers are dependent on androgens. Inhibitors of this cytochrome P450 are currently in clinical trials for prostate and breast cancer. We have crystals of the human enzyme in complex with one of the leading clinical trial candidates. This structure will allow us to improve current inhibitors and to use structure-based drug design to improve/design other inhibitors to increase selectivity and improve cancer treatment.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目前还没有这种参与雄激素（和雌激素）合成的重要酶的结构。 80%的前列腺癌依赖于雄激素。 这种细胞色素 P450 的抑制剂目前正在进行前列腺癌和乳腺癌的临床试验。 我们拥有与领先的临床试验候选者之一复合的人类酶晶体。 这种结构将使我们能够改进现有的抑制剂，并使用基于结构的药物设计来改进/设计其他抑制剂，以提高选择性并改善癌症治疗。