Molecular Target Focused Discovery of Anticancer Drugs

继续研究的非常有力和尖锐的目标将是加速的 新的和结构独特的抗癌候选药物的发现和临床前开发， 美国美国国家癌症研究所.重点将继续致力于小分子抗癌 从陆地节肢动物、海洋生物、微生物和植物中分离出的成分， 结构测定、合成和/或结构修饰。将特别强调 基于分子靶生物测定分离的新的可降解物质或随后 显示这种有效的抗血管生成、癌症血管靶向、微管蛋白和/或各种癌症相关的 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 异常强烈的放射性。将更加重视进一步的研究 这对于推进奥瑞他汀、苔藓抑素1、海兔司他汀和海兔司他汀的扩大临床试验是必要的。 我们发现的其他药物，如强效的癌症抗血管生成和血管靶向药物， combretastin（CA 4P、CA 1 P）等系列。只有那些来自确认的活性提取物的电极导线 节肢动物，海洋无脊椎动物，海洋和陆地植物，以及海洋和陆地 最有希望产生具有潜在临床活性的新药的微生物将被 追求。建议的继续研究将为DCTD/NCI选择 新的抗癌候选药物，并加快其临床试验的发展。总之， 拟议的研究将尖锐地瞄准发现和非常迅速地开发新的抗癌药物。 NCI计划的药物直接用于改善人类癌症治疗。

The very vigorous and sharply focused objective of the continuation research will be the accelerated discovery and preclinical development of new and structurally unique anticancer drug candidates for the U.S. National Cancer institute. Emphasis will continue to be devoted to small molecule anticancer constituents isolated from terrestrial arthropods, marine organisms, microorganisms and plants followed by structural determinations, syntheses and/or structural modifications. Special emphasis will be placed on new antineoplastic substances either isolated based on molecular target bioassays or subsequently displaying such potent antiangiogenesis, cancer vascular targeting, 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 the auristatins, bryostatin 1, the dolastatins, and others we discovered such as the powerful cancer antiangiogenesis and vascular targeting drugs in the combretastin (CA4P, CA1P) and other series. Only those leads from confirmed active extracts of arthropods, marine invertebrates, marine and terrestrial plants, and marine as well as terrestrial microorganisms that give maximum promise of yielding new drugs with potential clinical activity will be pursued. The proposed continuation research will provide great assistance to the DCTD/NCI in selecting new anticancer drugs candidates and speeding their development toward clinical trials. In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs direct at improving human cancer treatments.