BIOLOGICAL EVALUATION, ISOLATION, STRUCTURE, LARGE-SCALE EXTRACTION & SYNTHESIS

生物学评价、分离、结构、大规模提取

• 批准号: 6396806
• 负责人: TIMOTHY J HARRIS
• 金额: --
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6396806
• 关键词: DNA gyrase; DNA topoisomerases; antimitotics; antineoplastics; bioassay; biological products; chemical structure function; clone cells; cooperative study; cytotoxicity; disease /disorder model; drug design /synthesis /production; drug resistance; drug screening /evaluation; growth factor receptors; laboratory mouse; medicinal plants; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; oncogenes; plant extracts; protein tyrosine kinase; solvent extraction; tubulin; tumor suppressor genes

Plants have traditionally been one of man's richest sources of biologically active materials; over 25% of all prescriptions dispensed in the U.S. contain a plant derived active principle. In collaboration with the University of Illinois at Chicago and Research Triangle Institute, Bristol-Myers Squibb plans to identify, isolate and characterize novel plant derived anticancer agents. Bristol-Myers Squibb Pharmaceutical Research Institute is a part of one of the largest pharmaceutical companies in the world with a strong commitment and resources dedicated to natural products screening. With respect to the NCNPDDG in question, we plan to carry out the following specific aims. 1. To assay ca. 500 plant samples per year for cytotoxicity, interaction with specific oncogenes, enzymes and proteins of DNA metabolism. 2. To assist in selecting and prioritizing the most biologically significant leads. 3 To support bioassay-guided fractionation of the active constituents. 4. To participate in the isolation and structure elucidation of the active constituents. 5. To obtain sufficient amounts of active compounds, by extraction and purification or by partial or total synthesis, depending upon the complexity of the molecule in question. 6. To profile in vitro and in vivo the biological properties of lead compounds obtained from this program. 7. To carry out the large-scale isolation and/or synthesis and the preclinical drug development of lead candidates. Bristol-Myers Squibb has an outstanding track record in accomplishing this type of aim, having successfully brought to clinical trials over five anticancer agents in the past six to seven years and having successfully solved the taxol supply problem.

植物历来是人类最丰富的营养来源之一， 生物活性物质;占所有处方的25%以上 在美国，含有植物衍生的活性成分。合作 伊利诺伊大学芝加哥分校和三角研究所 研究所，百时美施贵宝计划确定，分离和 表征新的植物衍生的抗癌剂。Bristol-Myers Squibb 医药研究所是世界上最大的 制药公司在世界上有一个坚定的承诺， 专门用于天然产品筛选的资源。相对于 关于NCNPDDG，我们计划实现以下具体目标。 1.为了测定Ca.每年500个植物样本，用于细胞毒性、相互作用 与DNA代谢的特定致癌基因、酶和蛋白质有关。 2.为了帮助选择和优先考虑生物学上最 重要线索 3支持活性成分的生物测定指导分级。 4.参与该化合物的分离和结构鉴定， 活性成分 5.为了获得足够量的活性化合物，通过提取和 纯化或通过部分或全部合成，取决于所述方法。 分子的复杂性。 6.在体外和体内分析电极导线的生物学特性 从该方案中获得的化合物。 7.为了进行大规模分离和/或合成， 主要候选药物的临床前药物开发。百时美施贵宝公司已 在实现这类目标方面有着出色的记录， 年，五种抗癌药物成功进入临床试验 在过去的六到七年里， 供应问题。