Discovery of Anticancer Agents of Diverse Natural Origin

多种天然来源的抗癌剂的发现

• 批准号: 10621868
• 负责人: JAMES R FUCHS
• 金额: $ 143.93万
• 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/10621868
• 关键词: Antineoplastic Agents; Binding Proteins; Biological; Biological Assay; Biological Testing; Biometry; Biostatistics Core; Cancer cell line; Cells; Cessation of life; Chemicals; Chemistry; Chicago; Collection; Communication; Comprehensive Cancer Center; Consultations; Country; Coupled; Cyanobacterium; Databases; Decision Making; Developing Countries; Development; Disease; Doctor of Philosophy; Drug Industry; Drug Kinetics; Evaluation; Fiber; Formulation; Fractionation; Funding; Genomics; Goals; Human Resources; Illinois; In Vitro; Institution; Lead; Libraries; Lichen - organism; Malignant Neoplasms; Marketing; Metabolism; Methods; Modification; Molds; National Cancer Institute; National Center for Advancing Translational Sciences; Natural Compound; Natural Products; Neurofibromatosis 2; North Carolina; Ohio; Organism; Participant; Pediatric Hospitals; Pharmaceutical Chemistry; Plants; Play; Principal Investigator; Process; Provider; Regimen; Research; Research Personnel; Resistance; Resources; Role; Sampling; Solubility; Structure; Taxonomy; Testing; Therapeutic; Toxicology; United States; United States National Institutes of Health; Universities; Woman; Work; Xenograft procedure; analog; anticancer activity; antitumor drug; cancer therapy; chemotherapeutic agent; computerized; data management; drug development; drug discovery; experience; fungus; in vitro testing; in vivo; in vivo Bioassay; literature survey; meetings; men; novel; novel anticancer drug; programs; scale up; tumor; tumor growth

OVERALL 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.

总体项目摘要 在此计划项目续订应用程序中，申请人组代表了三个主要机构， 俄亥俄州立大学（OSU），伊利诺伊大学芝加哥大学（UIC）和北卡罗来纳大学 在格林斯伯勒（UNCG）。参与者将他们丰富的经验结合在一起 阐明天然产物的生物学评估，以开发合并的，综合的 发现新型抗癌剂的计划多种发育的抗癌药作为癌症 化学治疗剂。将在项目1（OSU）中研究的植物材料将通过既定 在Napralert数据库（项目2; UIC）的协助下，位于热带国家的植物学家和 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。获取的生物将在各种相关的电池中提取和评估 基于机制的基于细胞和肿瘤生长的相关测定目前在OSU（项目1），UIC （核心1），哥伦比亚大学（通过项目3）和其他外部合作者（通过OSU的核心A）。 将使用计算机化的OSU，UIC和UNCG在OSU，UIC和UNCG上删除已知的活性化合物 文献调查和LC-MS耦合到生物测定。生物测定指导的分馏将用于项目 1-3用于阐明主动原理。通过药用的主动天然产品的铅开发 化学和药代动力学相关的研究将在OSU促进的OSU（CORE 2）进行 生物统计学组（核心A）。因此，发现新颖的活性化合物将在我们的面板中进一步评估 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）。小组决定将 就可以进一步开发代理作为抗癌药物的进一步开发。更高级 生物学和毒理学测试的阶段将通过与药物发现研究所的磋商有助于 OSU综合癌症中心（通过核心A）该财团将与 NCI计划在发现过程中的官员，并计划定期举行关键科学人员的会议 （包括我们的外部和OSU内部科学咨询委员会），以增强沟通和决策 - 制作过程，由核心A组织。 化学修饰，合成以及体外和体内生物学评估以及总体项目数据 管理可用。该P01的总体目标是确定最终具有的铅化合物 治疗癌症的治疗价值。