DEVELOPING NEW SOURCES OF ANTICANCER DRUGS: ENDEMIC COASTAL MACROLICHENS AND THEIR ASCOMYCETES AND BASIDIOMYCETES MYCOBIONTS

开发抗癌药物新来源：地方性沿海大地衣及其子囊菌和担子菌菌体

• 批准号: 9440799
• 负责人: Alan Douglas Kinghorn
• 金额: $ 12.26万
• 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: 2007-09-14 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9440799
• 关键词: Antineoplastic Agents; Ascomycota; Basidiomycota; Binding Proteins; Biological; Biological Assay; Biological Testing; Biometry; Biostatistics Core; Cell Line; Cells; Cessation of life; Chemicals; Chemistry; Chicago; Chronic Lymphocytic Leukemia; Collection; Communication; Comprehensive Cancer Center; Country; Coupled; Cyanobacterium; Databases; Decision Making; Developing Countries; Development; Disease; Doctor of Philosophy; Drug Industry; Drug Kinetics; Evaluation; Fiber; Formulation; Fractionation; Funding; Goals; Histone Deacetylase; Human Resources; Illinois; In Vitro; Industrialization; Institution; Instruction; Lead; Libraries; Malignant Neoplasms; Metabolism; Methods; Modification; Molds; National Cancer Institute; Natural Products; North Carolina; Ohio; Organism; Participant; Pharmaceutical Chemistry; Pharmacologic Substance; Plants; Play; Principal Investigator; Process; Proteasome Inhibition; Regimen; Research; Research Personnel; Resistance; Resources; Role; Sampling; Small Cell Carcinoma; Solubility; Source; Structure; Supervision; Taxonomy; Testing; Toxicology; United States; Universities; Woman; Work; Xenograft procedure; analog; antitumor drug; base; chemotherapeutic agent; computerized; data management; drug discovery; experience; forest; fungus; in vitro testing; in vivo; in vivo Bioassay; literature survey; meetings; men; novel; novel anticancer drug; programs; scale up; screening; tumor; tumor growth

In this revised 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 continue 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 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 A), Columbia University (through Project 3), and a new pharmaceutical company partner, Eisai Inc., Andover, MA (through Core C 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 active principles. Lead development of active natural products via medicinal chemistry and pharmacokinetics- related studies will be conducted at OSU (Core B), facilitated by the OSU Biostatistics group (Core C). Novel, active compounds thus discovered will be further evaluated in our panel of in vitro and in vivo bioassays (Projects 1 and 3, Cores A and Eisai). Group decisions will be made regarding the further development of agents for potential use as anticancer agents. The more advanced states of biological and toxicological testing, as well as the procurement of larger quantities of lead compounds will be sponsored by Eisai (through Core C). The Consortium will work with the involvement of the NCI Program Director in the discovery process, and plans to hold regular meetings of key scientific personnel (inclusive of our External and OSU Internal Advisory panels) to enhance communication and decision-making processes, to be organized by Core C. Excellent facilities for the isplation, structure determination, chemical modification, synthesis, and in vitro and in vivo biological evaluation, and overall project data management are available. RELEVANCE (See instructions): Cancer is responsible for about one in every four deaths in the United States, and new treatments are urgently needed. It is the overall goal of the integrated studies in this renewal application to discover novel chemicals from selected tropical rainforest plants, as well as cyanobacteria and fungi, for development as cancer chemotherapeutic agents, particularly for tumors not cured by present treatment methods.

在本修订后的计划项目续期申请中，申请团体主要代表三个团体