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Discovery/Development of Anticancer Agents from Plants

植物抗癌剂的发现/开发

基本信息

批准号：
7154087
负责人：
FREDERICK Augustus VALERIOTE
金额：
$ 44.79万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-17 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7154087
关键词：
Agreement Agriculture Antineoplastic Agents Arizona Bilateral Biological Biological Assay Biological Factors Biological Products Biomass Bone Marrow Botanicals Cancer Center Chemicals Collaborations Collection Commit Crude Extracts Development Dose Drug Delivery Systems Drug Exposure Drug Formulations Drug Kinetics Fabaceae Fractionation Goals Hydroponics In Vitro Individual Investigation Laboratories Lead Literature Malignant Neoplasms Maximum Tolerated Dose Measures Mediation Methodology Methods Mus Nature Normal tissue morphology Numbers Pharmaceutical Preparations Pharmacology Plant Extracts Plant Roots Plants Principal Investigator Procedures Production Research Sampling Schedule Seeds Serum Solid Neoplasm Source Staging Stem cells System Testing Therapeutic Therapeutic Studies Therapy Clinical Trials Time Treatment Efficacy Tumor Volume Universities Ursidae Family Wit Work Xenograft procedure analytical method anticancer activity aqueous base cancer cell cytotoxic dosage drug clearance drug development in vivo man medical specialties novel pre-clinical programs research and development tumor

项目摘要

The goal of this project is the discovery and development of new anticancer agents with solid tumor activity from leads obtained from plants The need for this is significant given the paucity of anticancer agents active against the major solid tumors of man During the past 5 years, nearly 4000 crude plant extracts, from the laboratory of Dr Joseph Hoffmann at the University of Arizona, have been evaluated for solid tumor selectivity by Dr Fred Valeriote, now at the Josephine Ford Cancer Center The results of these studies have provided this project with 30 prioritized, primary hits to continue with isolation (through bioassay- directed fractionation) and identification of the active compound(s) from these plants over the next 5 years In order to accomplish the objectives, bulk collections will be made as needed or plants will be grown in experimental field plots to provide sufficient material for expanded testing both in vitro and in vivo Additional material will be generated through aeroponic/hydroponic systems, especially when root material is the primary source of the active compound(s) Also, 200 new plants will be collected each year with the new and old leads prioritized annually Six priority plants will be targeted for completion each year to generate at least 6 active compounds for both in vitro and in vivo testing Greater emphasis will be placed on novel compounds over known compounds with either new or known anticancer activity The anticancer drug development component will be carried out at the Josephine Ford Cancer Center The pure compound moves into formulation, pharmacology and therapeutic assessment There are three essential components to in vivo pharmacology testing development of analytical methods for chemical analysis of the new compounds, development of a suitable IV formulation through biopharmaceutical measures, and preliminary pharmacology testing for drug clearance and distribution Doses and target drug concentrations will be established in vitro Mice will bear bilateral tumors that have grown to 100 to 300 ram3 prior to initiation of dosing Doses of each agent contained in 0 2 ml volume for parenteral administration will be estimated from traditional dosage demands and dosages adjusted for in vitro pharmacology results The methodology for the study on therapeutic efficacy to test doses of compound, up to the maximum tolerated dose, in tumor- bearing mice (syngeneic with a murine tumor or xenografted wit

本项目的目标是发现和开发具有实体瘤活性的新型抗癌药物从植物中获得的铅考虑到抗癌剂活性的缺乏，在过去的5年里，近4000种天然植物提取物，从人类的主要实体肿瘤，亚利桑那大学约瑟夫·霍夫曼博士实验室的一项研究已经被评估为实体瘤现就职于约瑟芬福特癌症中心的弗雷德·瓦莱里奥特博士的选择性研究。我已经为这个项目提供了30个优先的，主要的命中继续隔离（通过生物测定- 定向分馏）和在未来5年内从这些植物中鉴定活性化合物为了实现这些目标，将根据需要进行大量收集，或在实验场图，为体外和体内扩展测试提供足够的材料。材料将产生通过气培/水培系统，特别是当根材料是此外，每年将收集200株新植物，和每年优先考虑的旧线索每年将有六个优先工厂完成，至少6种活性化合物用于体外和体内试验具有新的或已知抗癌活性的化合物优于已知化合物。开发部分将在约瑟芬福特癌症中心进行。进入配方，药理学和治疗评估有三个基本组成部分发展新的化学分析的分析方法，化合物，通过生物制药措施开发合适的IV制剂，药物清除和分布的药理学试验剂量和目标药物浓度将在体外建立的小鼠将带有双侧肿瘤，所述肿瘤在开始给药前已生长至100至300 μ m3。给药胃肠外给药的0 - 2 ml体积中所含的每种药物的剂量将根据传统剂量需求和针对体外药理学结果调整的剂量对测试剂量的化合物（高达最大耐受剂量）在肿瘤中的治疗功效的研究- 荷瘤小鼠（与鼠肿瘤同源或异种移植瘤）