Molecular Target Focused Discovery of Anticancer Drugs

抗癌药物的分子靶点聚焦发现

• 批准号: 7528174
• 负责人: GEORGE R PETTIT
• 金额: $ 38.13万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7528174
• 关键词: Address; 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; Goals; Grant; Health; Human; Indian Ocean; Inhibition of Cancer Cell Growth; Laboratories; Lactones; Malignant Neoplasms; Marine Invertebrates; Marines; Modification; Molecular Target; National Cancer Institute; Numbers; Oxis; Pharmaceutical Preparations; Phosphotransferases; Plants; Property; Protein Kinase C; Protein Tyrosine Kinase; Public Health; Research; Series; South American; Speed; Telomerase; Tubulin; United States; antiangiogenesis therapy; anticancer activity; base; bryostatin; cancer therapy; improved; marine organism; microorganism; novel; pre-clinical; programs; small molecule

DESCRIPTION (provided by applicant): As in the past 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 advance the expanding and vitally important clinical trials of the auristatins, bryostatin 1, the dolastatins, and others discovered in our laboratory such as the powerful cancer antiangiogenesis and vascular targeting drugs in the combretastatin (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 drug 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 directed at improving human cancer treatments. PUBLIC HEALTH RELEVANCE: In the coming year approximately 600,000 people will die of cancer in the United States alone. The discovery and development of more effective and curative anticancer drugs is a vital component in the global effort to address this devastating health problem. The goal of this project is the discovery and development of novel small molecules from terrestrial arthropods, marine organisms, microorganisms, and plants with sufficient antineoplastic activity to offer the potential for ultimate clinical activity against human cancer.

描述（由申请人提供）：与过去，连续研究的非常有力且浓重的目标将是对美国国家癌症研究所的新的和结构上独特的抗癌药物候选者的加速发现和临床前开发。重点将继续致力于从陆生节肢动物，海洋生物，微生物和植物中分离出的小分子抗癌成分，然后进行结构测定，合成和/或结构修饰。特殊重点将放在新的抗肿瘤物质上，要么是基于分子靶向生物测定的孤立的，或者随后显示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（细胞周期蛋白依赖性，蛋白质激酶C，蛋白激酶C，蛋白酶激酶和远距离型）的特性。将要进行进一步的研究，以进一步的研究，以促进极光蛋白，Bryostatin 1，dolastatins以及其他在我们的实验室中发现的其他临床试验，例如在Combretastatin（CA4P，CA1P）和其他系列中发现的强大的癌症抗静脉生成和血管靶向药物。只有那些来自节肢动物，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的积极提取物的铅提取物，这些物质最大程度地希望产生具有潜在临床活性的新药。拟议的延续研究将为DCTD/NCI提供大力的帮助，以选择新的抗癌药物候选者并加快其发展临床试验的发展。总而言之，拟议的研究将针对旨在改善人类癌症治疗的NCI计划的新抗癌药物的发现和快速开发。 公共卫生相关性：在来年，仅在美国，大约有60万人将死于癌症。在解决这一毁灭性健康问题的全球努力中，发现和开发更有效和治愈的抗癌药物是至关重要的组成部分。该项目的目的是从陆地节肢动物，海洋生物，微生物和具有足够抗塑性活性的植物发现和开发新的小分子，以提供对人类癌症的最终临床活性的潜力。