Directing the Mediator Complex: Bivalent approaches to Reconstituting or Inhibiti

描述(由申请人提供)：这个项目结合了三个不同研究人员的专业知识，协调解决了NCI挑衅性的问题#18：“是否有新的技术来抑制致癌表型所需的传统上‘不可用药’的靶分子，如转录因子？”为了解决这个问题，我们将开发三种不同的、但协同的化学物质，以提供干扰转录因子等不可药物靶标的新分子。同时，我们将评估他们对细胞内目标的访问，并定义编码细胞访问的结构特征。这些概念将在p53转录因子的背景下开发，P53转录因子是典型的抗癌靶点，它对介体复合体的MED17亚单位的影响。

DESCRIPTION (provided by applicant): This project combines the expertise of three different investigators in an orchestrated effort to address the NCI Provocative Question #18: "Are there new technologies to inhibit traditionally 'undruggable' target molecules, such as transcription factors, that are required for the oncogenic phenotype?" To address this question, we will develop three distinct, but synergistic, chemistries to provide new molecules that perturb undruggable targets such as transcription factors. In concert, we will evaluate their access to targets within cells and define the structural features that code for cellular access. These concepts will be developed in the context of the p53 transcription factor, a quintessential anti-cancer target, and its effects on the MED17 subunit of the Mediator complex.