Anticancer Leads from Marine Sponges and Marine Fungi

海洋海绵和海洋真菌的抗癌作用

• 批准号: 6924483
• 负责人: Phil Crews
• 金额: $ 19.01万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924483
• 关键词: Fungi; Porifera; antineoplastics; aquatic organism; biological products; biotechnology; cooperative study; drug discovery /isolation; high throughput technology; information retrieval; mass spectrometry; metabolomics; microorganism resource /registry; neoplasm /cancer chemotherapy; protein protein interaction; saltwater environment; small molecule; technology /technique development

As of 2004, there are more than 129 FDA approved small molecule drugs available for extending life expectancy in at least thirteen types of fatal cancers. However, based on the recent cancer statistics it is projected for 2004 that there will be 1,368,030 new cancer'cases and over 563,700 Americans are expected to succumb to this disease. Additional therapeutic interventions are needed for the treatment of cancer. This project uses target-based assays to discover compounds that will be relevant to treat the four most common solid tumor cancers such as colon/rectal, lung, breast and prostate, which together account for almost 70% of all cancer deaths in the U.S. The Crews component of the NCDDG will explore the natural products from a library of collected sponges and cultured fungi obtained from three sources: sponges, their surrounding water column, and deepwater sediments. A synergist investigation, capitalizing on the strengths of the four additional lab NCDDG programs, will be launched in pursuit of nine specific aims as follows. (1) To continue the study of Indo-Pacific sponges and extracts in our repository for novel biologically active small molecules (MW 400 - 2000) as a source of new anticancer lead compounds. (2) To collect unexplored sponges as a source of additional small molecules. (3) To create a fungal library for saltwater culture from sponges and their surrounding water column. (4) To create a fungal library for saltwater culture from deepwater sediments. (5) To utilize the NIBRI epigenetic and molecular target-based assays to continue the study of current and future active extracts. (6) To shorten the time from discovery of an active extract to defining its active constituents by creating peak libraries for high throughput screening (HTS) guided isolation, followed by state-of-the-art dereplication or structure elucidation. (7) To use Mass Spec approaches for database mining and metabolomic study, in order to expand the chemodiversity of structural lead compounds. (8) To engage in lead optimization. (9) To obtain patent coverage for important new active compounds.

截至2004年，有超过129种FDA批准的小分子药物可用于延长至少13种致命癌症的预期寿命。然而，根据最近的癌症统计数据，预计2004年将有1，368，030例新的癌症病例，预计将有超过563，700名美国人死于这种疾病。需要额外的治疗干预来治疗癌症。该项目使用基于靶点的分析来发现与治疗四种最常见的实体瘤癌症相关的化合物，如结肠/直肠癌，肺癌，乳腺癌和前列腺癌，这四种癌症加起来占近70%。 NCDDG的船员组成部分将探索从三个来源收集的海绵和培养真菌库中获得的天然产品：海绵，其周围的水柱和深水沉积物。一个可持续发展的调查，利用四个额外的实验室NCDDG计划的优势，将启动在追求九个具体目标如下。(1)继续研究印度太平洋海绵和提取物在我们的新的生物活性小分子（MW 400 - 2000）作为新的抗癌先导化合物的来源库。(2)收集未开发的海绵作为额外小分子的来源。(3)为了从海绵中建立一个用于盐水培养的真菌库， 它们周围的水柱(4)建立深海沉积物盐水培养真菌文库。(5)利用NIBRI表观遗传学和基于分子靶向的试验继续研究当前和未来的活性提取物。(6)通过创建高通量筛选（HTS）引导分离的峰库，然后进行最先进的去复制或结构解析，缩短从发现活性提取物到确定其活性成分的时间。(7)利用质谱方法进行数据库挖掘和代谢组学研究，以扩大结构先导化合物的化学多样性。(8)从事铅优化. (9)为重要的新活性化合物申请专利。