Molecular Target Focused Discovery of Anticancer Drugs

描述：发现结构新颖且可能非常重要的 从动物、植物和微生物来源的抗癌药物， 合成和/或结构修饰将形成尖锐聚焦的 美国国家癌症研究所（NCI）的这项研究的目的。 将特别强调新的可再生物质， 基于分子靶生物测定分离或随后显示这种 有效的抗血管生成、微管蛋白和/或各种癌症相关激酶 （细胞周期蛋白依赖性、蛋白激酶C、酪氨酸激酶和端粒酶）特性 以及异常强烈的抗氧化活性。进一步强调 将进行进一步的研究，以推动扩大 苔藓抑素1的临床试验，多拉司他汀，和其他我们发现这样的 抗血管生成药物考布他汀A-4磷酸盐。 有力的平行研究将强烈集中在隔离上， 表征和结构测定新的和潜在有用的 抗癌药物从确认的活性提取物的海洋无脊椎动物（和 脊椎动物），海洋和陆地植物，以及海洋和陆地 微生物的只有那些最有希望产生新的 具有潜在临床活性的药物将被追求。拟议研究 将为DCTD/NCI选择新的抗癌药物提供很大的帮助 候选人，并加快他们的临床试验的发展。总的来说， 拟议中的研究将以发现为目标， 为NCI项目开发新的抗癌药物， 人类癌症治疗。

DESCRIPTION: Discovery of structurally novel and potentially very important anticancer drugs from animal, plant and microorganism sources followed by their synthesis and/or structural modification will form the sharply focused objective of this research for the U.S. National Cancer Institute (NCI) . Special emphasis will be placed on new antineoplastic substances either isolated based on molecular target bioassays or subsequently displaying such potent antiangiogenesis, tubulin and/or various cancer-implicated kinase (cyclin-dependent, protein kinase C, tyrosine kinase and telomerase) properties as well as exceptionally strong antineoplastic activity. Additional emphasis will be placed on further research necessary to advancing the expanding clinical trials of bryostatin 1, the dolastatins, and others we discovered such as the powerful cancer antiangiogenesis drug combretastatin A-4 phosphate. vigorous parallel research will be strongly focused on the isolation, characterization, and structural determination of new and potentially useful anticancer drugs from confirmed active extracts of marine invertebrates (and vertebrates) , marine and terrestrial plants, and marine as well as terrestrial microorganisms. Only those species that give maximum promise of yielding new drugs with potential clinical activity will be pursued. The proposed research will provide great assistance to the DCTD/NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs directed at improving human cancer treatments.