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） 该 NCNPDDG 的长期目标是鉴定化合物 适合作为抗肿瘤药物开发。 这是由 1. 利用现有的、经过验证的检测方法来指导筛选/分离 新型 DNA 损伤剂和 DNA 拓扑异构酶 I、DNA 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. 开发新的基于机制的检测作为高通量初级筛选 对于具有治疗癌症潜在活性的天然产物， 包括增殖相关信号转导抑制剂（计划 1） 3. 分馏铅提取物并表征分离的天然产物 源自每个分析系统作为化学实体和生物实体 调解员（计划 2 和 3） 4. 制定和利用次要区分因素来指导重点关注的问题 预测的天然/产品/结构修饰化合物的鉴定 具有有用的抗肿瘤活性（方案 1 和 3） 5. 肿瘤细胞中大量制备和评估有前景的化合物 （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（项目 1-3）

项目成果

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

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

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

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 acylated oleanane triterpenoid from Couepia polyandra that inhibits the lyase activity of DNA polymerase beta.

一种来自 Couepia Polyandra 的新型酰化齐墩果烷三萜类化合物，可抑制 DNA 聚合酶 β 的裂解酶活性。

• DOI: 10.1021/np0301893
• 发表时间: 2003
• 期刊: Journal of natural products.
• 作者: PrakashChaturvedula,VS;Gao,Zhijie;Hecht,SidneyM;Jones,ShannonH;Kingston,DavidGI
• 通讯作者: Kingston,DavidGI