Discovery of Anticancer Agents of Diverse Natural Origin

多种天然来源的抗癌剂的发现

• 批准号: 10380980
• 负责人: Alan Douglas Kinghorn
• 金额: $ 15.48万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10380980
• 关键词: Administrative Supplement; Antineoplastic Agents; Biological; Biological Assay; Biological Testing; Biometry; Cells; Cessation of life; Chemicals; Chemistry; Chemotherapy-Oncologic Procedure; Chicago; Collection; Communication; Complex Mixtures; Comprehensive Cancer Center; Consultations; Country; Coupled; Crude Extracts; Cyanobacterium; Databases; Decision Making; Development; Drug Kinetics; Drug Targeting; Elements; Evaluation; Fractionation; Goals; Grant; Growth; High Pressure Liquid Chromatography; Human Resources; Illinois; In Vitro; Inflammasome; Institutes; Institution; Lead; Libraries; Lichen - organism; Malignant Neoplasms; Methods; Modification; Molds; Molecular Target; Natural Products; North Carolina; Ohio; Organism; Parents; Participant; Pathway interactions; Pharmaceutical Chemistry; Phytochemical; Plants; Process; Program Research Project Grants; Research; Sampling; Source; Speed; Structure; Taxonomy; Techniques; Testing; Therapeutic; Toxicology; United States; Universities; Work; base; cancer cell; cancer therapy; cancer type; cell type; chemotherapeutic agent; computerized; data management; drug discovery; experience; fungus; in vitro Assay; in vivo; in vivo Bioassay; literature survey; meetings; novel; novel anticancer drug; parent grant; programs; rare cancer; targeted cancer therapy; tumor; tumor growth

OVERALL P01 PROJECT SUMMARY In this Program Project renewal application, the applicant group is representative of three primary institutions, The Ohio State University (OSU), the University of Illinois at Chicago (UIC), and the University of North Carolina at Greensboro (UNCG). The participants have combined their vast experience in the isolation, structure elucidation, and biological evaluation of natural products, to the development of a consolidated, integrated program for the discovery of novel anticancer agents of diverse origin for development as cancer chemotherapeutic agents. Plant materials to be studied in Project 1 (OSU) will be collected by established botanists located in tropical countries with the assistance of the NAPRALERT database (Project 2; UIC), and lichens and their fungal associates (Project 1), cyanobacteria (Project 2) and filamentous fungi (Project 3; UNCG) will also be accessed. Organisms acquired will be extracted and evaluated in a diverse battery of relevant mechanism-based, cell-based, and tumor-growth related assays currently operational at OSU (Project 1), UIC (Core 1), Columbia University (through Project 3), and via other external collaborators (through Core A at OSU). Dereplication of known active compounds will be accomplished at OSU, UIC, and UNCG using computerized literature surveys and LC-MS coupled to bioassays. Bioassay-directed fractionation will be employed in Projects 1-3 for the elucidation of the active principles. Lead development of active natural products via medicinal chemistry and pharmacokinetics-related studies will be conducted at OSU (Core 2), facilitated by the OSU Biostatistics group (Core A). Novel, active compounds thus discovered will be further evaluated in our panel of in vitro and in vivo bioassays (Projects 1 and 3, Core A, and some external collaborators). Group decisions will be made regarding the further development of agents for potential use as anticancer agents. The more advanced stages of biological and toxicological testing will be aided through consultation with the Drug Discovery Institute of the OSU Comprehensive Cancer Center (through Core A). The Consortium will work with the involvement of the NCI Program Official in the discovery process, and plans to hold regular meetings of key scientific personnel (inclusive of our External and OSU Internal Scientific Advisory Boards) to enhance communication and decision- making processes, to be organized by Core A. Excellent facilities for the isolation, structure determination, chemical modification, synthesis, and in vitro and in vivo biological evaluation, and overall project data management are available. The overarching goal of this P01 is to identify lead compounds that ultimately have therapeutic value for the treatment of cancer.

P01 项目总体概要 在本计划项目续展申请中，申请群体由三个主要机构代表， 俄亥俄州立大学 (OSU)、伊利诺伊大学芝加哥分校 (UIC) 和北卡罗来纳大学 在格林斯博罗（UNCG）。参与者结合了他们在隔离、结构方面的丰富经验 天然产物的阐明和生物学评价，以开发综合的、综合的 发现不同来源的新型抗癌剂以发展为癌症的计划 化疗剂。项目 1（OSU）中要研究的植物材料将由已建立的机构收集 在 NAPRALERT 数据库（项目 2；UIC）的帮助下，位于热带国家的植物学家，以及 地衣及其真菌伙伴（项目 1）、蓝细菌（项目 2）和丝状真菌（项目 3）； UNCG）也将被访问。获得的生物体将被提取并在多种相关的电池中进行评估 基于机制、基于细胞和肿瘤生长相关的检测目前在 OSU（项目 1）、UIC 运行 （核心 1）、哥伦比亚大学（通过项目 3）以及其他外部合作者（通过 OSU 的核心 A）。 已知活性化合物的去重复将在 OSU、UIC 和 UNCG 使用计算机完成 文献调查和 LC-MS 与生物测定相结合。项目中将采用生物测定指导的分馏 图1-3用于阐明有效原理。通过药物主导活性天然产品的开发 化学和药代动力学相关研究将在 OSU（核心 2）进行，由 OSU 协助 生物统计学组（核心A）。由此发现的新型活性化合物将在我们的小组中进一步评估 体外和体内生物测定（项目 1 和 3、核心 A 和一些外部合作者）。团体决策将 关于进一步开发可能用作抗癌剂的药剂。更先进的 生物和毒理学测试阶段将通过与药物发现研究所的协商得到帮助 俄勒冈州立大学综合癌症中心（通过核心 A）。该联盟将在以下各方的参与下开展工作 NCI 项目官员参与发现过程，并计划定期召开关键科学人员会议 （包括我们的外部和 OSU 内部科学顾问委员会）以加强沟通和决策- 制作过程，由核心 A 组织。用于隔离、结构测定、 化学修饰、合成、体内外生物学评价、项目总体数据 管理可用。该 P01 的总体目标是确定最终具有的先导化合物 对于治疗癌症有治疗价值。