Transcription Factor GABP as an Antitumor Target

转录因子 GABP 作为抗肿瘤靶点

• 批准号: 6331108
• 负责人: SERGUEI Y GOLOVINE
• 金额: $ 10万
• 依托单位: PINNACLE PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-03 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6331108
• 关键词: antineoplastics; binding proteins; biological products; biotherapeutic agent; chemical registry /resource; drug screening /evaluation; fluorescence; high throughput technology; protein protein interaction; protein structure function; technology /technique development; transcription factor

DESCRIPTION: (provided by applicant) Recent developments in genomics and basic molecular biology have greatly increased the number of potential targets for antitumor therapy. These targets need validation before it is feasible to carry agents that act on them through the drug development process. The long-term goal of this SBIR program is to identify novel antitumor agents from natural product and synthetic chemical libraries. GA binding protein (GABP), also known as Nuclear Respiratory Factor - 2 (NRF-2), plays a crucial role in the coordination of oxidative metabolism and mitochondrial biogenesis. The objective of this application is to develop an in vitro assay to detect inhibitors of GABP function. The specific aims are: First, to develop a fluorescence-based assay for GABP function that is adaptable to a high-throughput format, and, secondly, to screen Pinnacle's natural product and compound libraries to identify entities that inhibit GABP function. In future work, these inhibitors will serve as tool compounds for testing the Central Hypothesis of this program: that compounds that act on GABP in vitro will be inhibitory to tumor cells, either alone or in combination with other agents. PROPOSED COMMERCIAL APPLICATION: This technology is intended to provide tool compounds for verification of GABP as an antitumor target.

描述：（由申请人提供） 基因组学和基础分子生物学的最新发展极大地促进了 增加了抗肿瘤治疗的潜在靶标的数量。这些目标 在携带对它们起作用的药剂可行之前需要验证 药物开发过程。该 SBIR 计划的长期目标是 从天然产物和合成化学品中鉴定新型抗肿瘤剂 图书馆。 GA结合蛋白（GABP），也称为核呼吸因子 - 2 (NRF-2)，在氧化代谢的协调中起着至关重要的作用 和线粒体生物发生。 该应用程序的目标是开发 检测 GABP 功能抑制剂的体外测定。具体目标 是：首先，开发一种基于荧光的 GABP 功能测定方法，即 适应高通量格式，其次，筛选 Pinnacle 的 用于识别抑制 GABP 的实体的天然产物和化合物库 功能。 在未来的工作中，这些抑制剂将作为工具化合物来测试 该程序的中心假设：体外作用于 GABP 的化合物 单独或与其他药物联合使用时，对肿瘤细胞具有抑制作用 代理。 拟议的商业应用： 该技术旨在为 GABP 验证提供工具化合物 抗肿瘤靶点。