NATURAL PRODUCTS DISCOVERY - NUCLEAR AND SIGNALING TARGE

天然产品的发现 - 核和信号目标

• 批准号: 6772479
• 负责人: Sidney Michael Hecht
• 金额: $ 96.99万
• 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 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772479
• 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） 本NCNPDDG的长期目标是鉴定化合物 适合开发为抗肿瘤剂。 这项工作将由 1.利用现有的、经验证的检测方法指导筛选/分离 新的DNA损伤剂和DNA拓扑异构酶I、DNA 拓扑异构酶II、DNA聚合酶B和Myt 1激酶（程序1、2和3） 2.开发新的基于机制的检测方法作为高通量初级筛选 对于在癌症治疗中具有潜在活性的天然产物， 包括增殖相关信号转导的抑制剂（方案1） 3.分离铅提取物和表征分离的天然产物 作为化学实体和生物实体衍生自每个测定系统 调解员（方案2和3） 4.开发和利用二级鉴别器， 预测的天然/产品/结构改性化合物的鉴定 具有有用的抗肿瘤活性（程序1和3） 5.在肿瘤细胞中大量制备和评价有希望的化合物 (for机制，生化药理学，与已知的 药物）和动物肿瘤模型（程序1-3）

项目成果

Bioactive compounds from Combretum erythrophyllum.

来自红叶风车草的生物活性化合物。

• DOI: 10.1021/np9904410
• 发表时间: 2000
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Schwikkard,S;Zhou,BN;Glass,TE;Sharp,JL;Mattern,MR;Johnson,RK;Kingston,DG
• 通讯作者: Kingston,DG

Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.

• DOI: 10.1021/np000058r
• 发表时间: 2000-07
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Bing-Nan Zhou;Jeannine M. Hoch;Randall K. Johnson;Michael R. Mattern;Wai-Kwong Eng;Ji Ma;Sidney M. H

Isolation and biochemical characterization of a new topoisomerase I inhibitor from Ocotea leucoxylon.

• DOI: 10.1021/np990442s
• 发表时间: 2000-01
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Bing-Nan Zhou;Randall K. Johnson;Michael R. Mattern;Xiangyang Wang;Sidney M. Hecht;Hans T. Beck;A. Ortiz;David G. I. Kingston

Halenaquinone and xestoquinone derivatives, inhibitors of Cdc25B phosphatase from a Xestospongia sp.

• DOI: 10.1016/j.bmc.2004.11.039
• 发表时间: 2005-02-15
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY
• 影响因子: 3.5
• 作者: Cao, SG;Foster, C;Kingston, DGI
• 通讯作者: Kingston, DGI

A new ursane triterpene from Monochaetum vulcanicum that inhibits DNA polymerase beta lyase.

一种来自 Monchaetum vulcanicum 的新乌苏烷三萜，可抑制 DNA 聚合酶 β 裂合酶。

• DOI: 10.1021/np030531b
• 发表时间: 2004
• 期刊: Journal of natural products.
• 作者: Chaturvedula,VSPrakash;Gao,Zhijie;Jones,ShannonH;Feng,Xizhi;Hecht,SidneyM;Kingston,DavidGI
• 通讯作者: Kingston,DavidGI