Molecular Target Focused Discovery of Anticancer Drugs

抗癌药物的分子靶点聚焦发现

• 批准号: 7476037
• 负责人: GEORGE R PETTIT
• 金额: $ 49.78万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476037
• 关键词: African; Animals; Antineoplastic Agents; Area; Arthropods; Asians; Biological Assay; Blood Vessels; Cancer cell line; Clinical; Clinical Trials; Combretastatin; Combretastatin A4 Phosphate; Country; Cyclin-Dependent Kinases; Development; Dolastatin Compound; Drug Delivery Systems; Evaluation; Expeditions; Grant; Human; Indian Ocean; Institutes; Lactones; Malignant Neoplasms; Marine Invertebrates; Marines; Modification; Molecular Target; National Cancer Institute; Numbers; Pharmaceutical Preparations; Phosphotransferases; Plants; Property; Protein Kinase C; Protein Tyrosine Kinase; Research; Series; South American; Speed; Telomerase; Tubulin; antiangiogenesis therapy; base; bryostatin; cancer therapy; improved; marine organism; microorganism; pre-clinical; programs; small molecule

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.

连续研究的非常有力和集中的目标将是加速的 新的和结构上独特的抗癌药物候选者的发现和临床前开发 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来的成分 结构确定，合成和/或结构修饰。特别重点将放在 新的抗肿瘤物质是基于分子靶标的分离的，或者随后的 表现出这种有效的抗血管生成，癌症血管靶向，微管蛋白和/或各种癌症刺激性 激酶（依赖细胞周期蛋白，蛋白激酶C，酪氨酸激酶和端粒酶）的性质以及特性 异常强的抗塑性活性。其他重点将放在进一步的研究上 为了推进Auristatins的扩展临床试验，Bryostatin 1，Dolastatins和 我们发现的其他人，例如强大的癌症抗血管生成和血管靶向药物 combretastin（CA4P，CA1P）和其他系列。只有那些来自确认的活性提取物的引线 节肢动物，海洋无脊椎动物，海洋和陆地植物以及海洋以及陆地 微生物具有最大的承诺，即产生潜在临床活性的新药将是 追捕。拟议的延续研究将为DCTD/NCI提供大力的帮助 新的抗癌药物候选物，并加快其发展为临床试验。总而言之， 拟议的研究将针对新抗癌的发现和非常快速的发展 NCI计划的药物直接改善人类癌症治疗。