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: 5207662
• 负责人: TIMOTHY J HARRIS
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5207662
• 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资源之一 生物活性物质；超过 25% 的处方 在美国含有植物衍生的活性成分。合作中 与伊利诺伊大学芝加哥分校和三角研究中心合作 百时美施贵宝研究所计划识别、隔离和 表征新型植物源抗癌剂。百时美施贵宝 药物研究所是最大的药物研究所之一的一部分 世界各地的制药公司都做出了坚定的承诺并 致力于天然产物筛选的资源。相对于 针对NCNPDDG的问题，我们计划实现以下具体目标。 1. 测定约。每年 500 个植物样本用于细胞毒性、相互作用 具有DNA代谢的特定癌基因、酶和蛋白质。 2. 协助选择和优先考虑最具生物学意义的 重要的线索。 3 支持活性成分的生物测定指导分级分离。 4. 参与该物质的分离和结构解析 活性成分。 5. 通过提取和提取来获得足够量的活性化合物 纯化或部分或全合成，取决于 相关分子的复杂性。 6. 分析铅的体外和体内生物学特性 从该程序获得的化合物。 7. 进行大规模分离和/或合成以及 主要候选药物的临床前开发。百时美施贵宝有 在实现此类目标方面拥有出色的记录， 成功将五种抗癌药物进入临床试验 过去六七年，成功解决了紫杉醇 供应问题。