• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Targeting the dimerization of ERBB receptor tyrosine kinases.
【24h】

Targeting the dimerization of ERBB receptor tyrosine kinases.

机译：靶向ERBB受体酪氨酸激酶的二聚化。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The epidermal growth factor receptor (EGFR) is a membrane receptor tyrosine kinase whose over-activation has been implicated to cause many human cancers. Novel strategies to inhibit the activation of EGF receptors other than the conventional antibody-based and tyrosine kinase inhibitors are virtually non-existent but could provide benefits both in the laboratory and clinical settings. In an effort to expand the current approaches, this thesis focused on targeting the homodimerization of the EGF receptors themselves and the heterodimerization of EGF receptors with the related ErbB2 receptor. Three subprojects were completed in the process. The first project explored the feasibility of inhibiting the EGF receptor by targeting receptor dimerization with small molecules. Two lead compounds were initially predicted by virtual screening the NCI compound library, and were biochemically characterized. The benefit gained from the application of virtual screening in this project initiated another project to enhance the accessibility of virtual screening within the non-computational community. The OpenScreening project utilizes distributed computing resources and provides open-access screening server at: http://omg.phy.umassd.edu/xvhts. A final project identified the structural mechanism that may explain the observed preference of EGFR-ErbB2 heterodimerization over EGFR homodimerization. Key residues were computationally predicted and biochemically tested to reveal critical dimerization interface.
机译：表皮生长因子受体（EGFR）是一种膜受体酪氨酸激酶，其过度活化与多种人类癌症有关。除了传统的基于抗体的抗体和酪氨酸激酶抑制剂外，目前还没有其他抑制EGF受体活化的新策略，但可以在实验室和临床环境中发挥作用。为了扩展当前的方法，本论文集中于靶向EGF受体自身的同二聚化以及EGF受体与相关的ErbB2受体的异二聚化。在此过程中完成了三个子项目。第一个项目探讨了通过靶向小分子受体二聚化来抑制EGF受体的可行性。通过虚拟筛选NCI化合物库初步预测了两种先导化合物，并对其进行了生化表征。在该项目中使用虚拟筛选所获得的收益启动了另一个项目，以提高虚拟筛选在非计算社区中的可访问性。 OpenScreening项目利用分布式计算资源，并在以下位置提供开放式访问筛选服务器：http://omg.phy.umassd.edu/xvhts。最终项目确定了可以解释观察到的EGFR-ErbB2异二聚体优先于EGFR同二聚化的结构机制。对关键残基进行了计算预测和生化测试，以揭示关键的二聚化界面。

著录项

  • 作者

    Yang, Robert Yunchuan.;

  • 作者单位

    Washington University in St. Louis.;

  • 授予单位 Washington University in St. Louis.;
  • 学科 Biology Molecular.;Biology Cell.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 145 p.
  • 总页数 145
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:38:25

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号