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: 3731078
• 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
• 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/3731078
• 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.

传统上，植物是人类的最丰富来源之一 生物活性材料；所有处方的25％以上 在美国，包含一种派生的活性原则。合作 与伊利诺伊大学的芝加哥大学和研究三角 Bristol-Myers Squibb研究所计划识别，隔离和 表征新型植物衍生抗癌剂。布里斯托尔（Bristol Myers）squibb 制药研究所是最大的一部分之一 世界上拥有坚定承诺的制药公司 专门用于天然产品筛查的资源。关于 NCNPDDG中，我们计划执行以下特定目标。 1。分析约每年500种植物样品，用于细胞毒性，相互作用 具有特定的癌基因，DNA代谢的酶和蛋白质。 2。协助选择和优先级的生物学优先级 重要的潜在客户。 3支持活性成分的生物测定指导分馏。 4。参与隔离和结构阐明 活性成分。 5。通过提取获得足够量的活性化合物 纯化或部分或全合成，具体取决于 所讨论的分子的复杂性。 6。要在体外和体内介绍铅的生物学特性 从该程序获得的化合物。 7。进行大规模隔离和/或合成以及 铅候选者的临床前药物开发。布里斯托尔（Bristol Myers Squibb）拥有的 实现这类目标的出色记录， 成功地进行了五个抗癌剂的临床试验 过去六到七年，并成功解决了紫杉醇 供应问题。