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

植物历来是人类最丰富的营养来源之一 生物活性物质；超过25%的处方配药 在美国含有一种植物衍生的活性成分。在协作中 与伊利诺伊大学芝加哥分校和研究三角 百时美施贵宝计划识别、隔离和 表征新型植物来源的抗癌药物。百时美施贵宝 医药研究所是世界上最大的医药研究所之一 世界上的制药公司有着坚定的承诺和 致力于天然产品筛选的资源。关于 关于NCNPDDG，我们计划实现以下具体目标。 1.每年检测约500个植物样本的细胞毒性、相互作用 具有DNA代谢的特定癌基因、酶和蛋白质。 2.帮助选择和优先选择最具生物学意义的 重大线索。 3支持以生物测定为导向的活性成分分级。 4.参与分离和结构鉴定 活性成分。 5.为了获得足够数量的活性化合物，通过提取和 提纯或部分或全部合成，取决于 有问题的分子的复杂性。 6.测定铅的体内外生物学特性 从这个程序中获得的化合物。 7.进行大规模分离和/或合成， 临床前药物开发的领先候选者。百时美施贵宝 在实现这类目标方面有出色的记录，具有 年成功将五种抗癌药物投入临床试验 在过去的六到七年里，成功地解决了紫杉醇 供应问题。

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.