Discovery/Development of Anticancer Agents from Plants

超出所提供的空间-该项目的目标是发现和开发新的抗癌剂与实体肿瘤活性从铅获得的植物这需要这是显着的抗癌剂的缺乏积极对主要实体肿瘤的人在过去的5年中，近4000粗植物提取物，从实验室博士约瑟夫霍夫曼在亚利桑那大学，现就职于约瑟芬福特癌症中心的Fred Valeriote博士已经对实体瘤的选择性进行了评估。这些研究的结果为该项目提供了30个优先的主要目标，以继续进行分离（通过生物测定定向分级分离）和在未来5年内从这些植物中鉴定活性化合物。为了实现目标，将根据需要进行大量收集或将植物生长在实验田间地块中以提供足够的材料用于体外和体内的扩展测试。另外的材料将通过气培法/水培法系统产生，特别是当根材料是活性化合物的主要来源时。此外，每年将收集200株新植物，每年优先考虑新的和旧的先导化合物。每年将有6株优先植物完成，以产生至少6种活性化合物，用于体外和体内测试。抗癌活性抗癌药物开发部分将在Josephine福特癌症中心进行纯化合物进入制剂、药理学和治疗评估体内药理学测试有三个基本部分：开发用于新化合物的化学分析的分析方法，通过生物制药措施开发合适的IV制剂，以及药物清除和分布的初步药理学试验。剂量和目标药物浓度将在体外确定。小鼠将带有双侧肿瘤，在开始给药前已生长至100至300 μ m 3。传统的剂量需求和根据体外药理学结果调整的剂量研究化合物的试验剂量，直至最大耐受剂量，在荷瘤小鼠（与鼠肿瘤同源或异种移植）中，PERFORMANCE SITE =====================================

EXCEED THE SPACE PROVIDED -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 PERFORMANCE SITE ========================================Section End===========================================