NATURAL PRODUCTS DISCOVERY - NUCLEAR AND SIGNALING TARGE

描述：(申请人描述) NCNPDDG的长期目标是鉴定化合物 适合作为抗肿瘤药物开发。这将通过以下方式完成 1.利用现有的、经过验证的化验方法指导筛选/分离 新型DNA损伤剂和DNA拓扑异构酶I抑制剂 拓扑异构酶II、DNA聚合酶B和Myt1激酶(程序1、2和3) 2.开发新的基于机理的分析方法，作为高通量的初级筛选 对于具有潜在癌症治疗活性的天然产品， 包括与增殖相关的信号转导的抑制剂(方案1) 3.铅萃取物的分级和分离天然产物的特征 作为化学实体和生物实体来自每一种分析系统 调解人(方案2和方案3) 4.开发和利用次级鉴别器来指导有重点的 预测的天然/产物/结构修饰化合物的鉴定 具有有用的抗肿瘤活性(方案1和方案3) 5.大量制备和鉴定在肿瘤细胞中具有应用前景的化合物。 (对于机制、生化药理学、与已知的相互作用 抗肿瘤药物)和动物肿瘤模型(程序1-3)

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)