NATURAL PRODUCTS DISCOVERY - NUCLEAR AND SIGNALING TARGE

天然产品的发现 - 核和信号目标

• 批准号: 6375851
• 负责人: Sidney Michael Hecht
• 金额: $ 87.63万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375851
• 关键词: antineoplastics; aquatic organism; biological products; drug screening /evaluation; enzyme inhibitors; plant extracts

DESCRIPTION: (Applicant's Description) The long term objective of this NCNPDDG is the identification of compounds suitable for development as antitumor agents. This is to be done by 1. utilizing existing, validated assay to guide the screening/isolation of novel DNA damaging agents, and inhibitors of DNA topoisomerase I, DNA topoisomerase II, DNA polymerase B and Myt1 kinase (Programs 1, 2 and 3) 2. developing new mechanism-based assays as high-throughput primary screens for natural products with potential activity in the treatment of cancer, including inhibitors of proliferation-linked signal transduction (Program 1) 3. fractionating lead extracts and characterizing isolated natural products derived from each of the assay systems as chemical entities and biological mediators (Programs 2 and 3) 4. developing and utilizing secondary discriminators to guide the focused identification of natural/products/structurally modified compounds predicted to have useful antitumor activity (Programs 1 and 3) 5. preparing in quantity and evaluating promising compounds in tumor cells (for mechanism, biochemical pharmacology, interaction with known antineoplastic agents) and in animal tumor models (Programs 1-3)

描述：（申请人的描述） 该NCNPDG的长期目标是化合物的识别 适合作为抗肿瘤剂的发育。 这是由 1。利用现有的，经过验证的测定来指导筛选/隔离 新型DNA损伤剂和DNA拓扑异构酶I的抑制剂，DNA 拓扑异构酶II，DNA聚合酶B和MYT1激酶（程序1、2和3） 2。开发新的基于机制的测定作为高通量主要屏幕 对于具有潜在活性在癌症治疗中的天然产物， 包括增殖连锁信号转导的抑制剂（程序1） 3。分馏铅提取物和表征孤立的天然产物 从每个测定系统作为化学实体和生物学衍生 调解员（计划2和3） 4.开发和利用次级歧视者指导专注 预测天然/产品/结构修饰的化合物的鉴定 具有有用的抗肿瘤活动（程序1和3） 5。数量准备并评估肿瘤细胞中有希望的化合物 （用于机理，生化药理学，与已知的相互作用 抗肿瘤剂）和动物肿瘤模型（程序1-3）