Molecular Target Focused Discovery of Anticancer Drugs

继续研究的非常有力和聚焦的目标将是加速 新的、结构独特的抗癌候选药物的发现和临床前开发 美国国家癌症研究所。重点将继续放在小分子抗癌上 从陆地节肢动物、海洋生物、微生物和植物中分离出的成分其次是 结构确定、合成和/或结构修改。我们将特别强调 基于分子靶标生物测定或随后分离的新抗肿瘤物质 显示出如此强大的抗血管生成、肿瘤血管靶向、微管蛋白和/或各种与癌症有关的 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)的性质以及 特别强的抗肿瘤活性。其他重点将放在进一步的研究上。 对推进金雀异黄素、Bryostatin 1、Dolastatins和 我们发现的其他药物，如强大的癌症抗血管生成和血管靶向药物 康瑞汀(CA4P、CA1P)等系列。只有那些来自确认的有效提取物的线索 节肢动物、海洋无脊椎动物、海洋和陆地植物、海洋和陆地植物 最有希望产生具有潜在临床活性的新药的微生物将是 被追捕。拟议的继续研究将为DCTD/NCI选择 新的抗癌候选药物并加快其临床试验的发展。总而言之， 拟议的研究将尖锐地瞄准新的抗癌药物的发现和快速发展 NCI项目的药物旨在改善人类癌症的治疗。

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.