Directing the Mediator Complex: Bivalent approaches to Reconstituting or Inhibiti

指导介体复合体：重建或抑制的二价方法

基本信息

批准号：
8895755
负责人：
Alanna Schepartz
金额：
$ 13.19万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8895755
关键词：
Address Adopted Affinity Binding Biological Assay Biology Cell Line Cells Chemistry Code Complex Cytosol Data Diffuse Diffusion Drug Tolerance Drug resistance Early Endosome Endocytosis Endosomes Enzymes Exhibits Gene Expression Generations Genes Genetic Transcription Genome Goals Growth H1299 Human In Vitro Knowledge Ligands MDA MB 231 Malignant Neoplasms Mediator of activation protein Membrane Molecular Mus Oncogenic Peptides Phenotype Protein p53 Research Personnel Structure System TP53 gene Technology Therapeutic Therapeutic Intervention Therapeutic Uses Ursidae Family anticancer research base cancer cell design fitness gain of function inhibitor/antagonist mimicry mutant new technology novel strategies reconstitution scaffold small molecule transcription factor tumor

Address Adopted Affinity Binding Biological Assay Biology Cell Line Cells Chemistry Code Complex Cytosol Data Diffuse Diffusion Drug Tolerance Drug resistance Early Endosome Endocytosis Endosomes Enzymes Exhibits Gene Expression Generations Genes Genetic Transcription Genome Goals Growth H1299 Human In Vitro Knowledge Ligands MDA MB 231 Malignant Neoplasms Mediator of activation protein Membrane Molecular Mus Oncogenic Peptides Phenotype Protein p53 Research Personnel Structure System TP53 gene Technology Therapeutic Therapeutic Intervention Therapeutic Uses Ursidae Family anticancer research base cancer cell design fitness gain of function inhibitor/antagonist mimicry mutant new technology novel strategies reconstitution scaffold small molecule transcription factor tumor

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项目摘要

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.

描述（由申请人提供）：该项目结合了三个不同研究人员的专业知识，以解决NCI挑衅性问题18：“是否有新技术可以抑制传统上“不可能”的目标分子（例如转录因素），例如转录因素，这些因素是癌症典型的表型吗？”为了解决这个问题，我们将开发三种不同但协同的化学物质，以提供新的分子，这些分子扰动不良靶标，例如转录因子。在一致的情况下，我们将评估它们在细胞内的目标的访问，并定义编码蜂窝访问的结构特征。这些概念将在p53转录因子，典型的抗癌目标及其对介体复合物的Med17亚基的影响中开发。