STRUCTURE OF HUMAN MEMBRANE CYTOCHROME P450 INVOLVED IN ANDROGEN BIOSYNTHESIS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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的抑制剂目前正在前列腺癌和乳腺癌的临床试验中。 我们有一种人体酶的晶体与一种领先的临床试验候选物相结合。 这种结构将使我们能够改进目前的抑制剂，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。

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.