Antitumor-Antibiotics from Marine Microorganisms

来自海洋微生物的抗肿瘤抗生素

• 批准号: 7909499
• 负责人: William Fenical
• 金额: $ 9.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909499
• 关键词: Actinobacteria class; Actinomyces; Biological; Biological Assay; Cell Line; Cells; Ceramidase; Collaborations; Communicable Diseases; DNA Modification Methylases; Drug resistance; Evaluation; Goals; Growth Factor; Habitats; Histocompatibility Testing; In Vitro; Institution; Insulin-Like Growth Factor I; Malignant Neoplasms; Marines; Modeling; Mus; Oceanography; Pharmacologic Substance; Research Institute; Screening procedure; Solid Neoplasm; Source; Transferase; Yeasts; antineoplastic antibiotics; arginine methyltransferase; base; efflux pump; in vivo; inhibitor/antagonist; leukemia; microorganism; novel; pathogen; repaired; salinosporamide A

This is a competitive renewal application to continue to explore marine microorganisms as a new source for antitumor-antibiotics. The proposed project would continue as a collaboration between chemists and microbiologists at the Scripps Institution of Oceanography in La Jolla, CA. and cancer biologists at the Bristol-Myers Squibb Pharmaceutical Research Institute in Princeton, NJ. Studies proposed for the renewal period include the following: - The isolation, cultivation and biological evaluation of marine microorganisms from diverse habitats. The focus of the renewal application will be on 7 new groups of obligate marine actinomycetes (Salinospora, Marinomyces, and the MAR 3-7 groups) discovered during the past 24 months. - Overall, to continue to isolate and describe new molecules which show novel mechanisms of action in cancer-relevant, mechanism-based screens, show in vitro tissue type selectivity in the NCI 60 cell line and BMS ODCA panels, and to subsequently investigate their in vivo efficacies. - To focus a screening effort on the new cancer relevant targets IGF-1 Growth Factor, DMA Methyl Transferase-1 (DNMT-1), CoactivatorAssociated Arginine Methyltransferase (CARM-1) and Ceramidase, and on yeast selective DMA repair and cell checkpoint targets. These goals will also be supplemented at SIO with several assays which focus on infectious diseases (screening against drug resistant pathogens and for inhibitors of two selected bacterial efflux pumps). - To continue to advance previous discoveries (Salinosporamide A, Halimide, Sargassamide A and several other molecules) for in vivo evaluation in the BMS P388 and L1210 leukemias and the murine solid tumor models M109, Mam16/C and M50766.

这是一个竞争性的更新应用程序，旨在继续探索海洋微生物作为新的 抗肿瘤抗生素的来源。拟议的项目将继续作为化学家之间的合作 以及加利福尼亚州拉霍亚斯克里普斯海洋学研究所的微生物学家。和癌症生物学家 位于新泽西州普林斯顿的百时美施贵宝制药研究所。拟议更新的研究 期间包括以下内容： - 来自不同栖息地的海洋微生物的分离、培养和生物学评价。这 更新申请的重点将是 7 个新的专性海洋放线菌类群（盐孢菌属、 Marinomyces 和 MAR 3-7 群）是在过去 24 个月内发现的。 - 总体而言，继续分离和描述新分子，这些分子显示出新的作用机制 癌症相关、基于机制的筛选，显示 NCI 60 细胞系的体外组织类型选择性， BMS ODCA 面板，并随后研究其体内功效。 - 将筛选工作的重点放在新的癌症相关目标 IGF-1 生长因子、DMA 甲基上 转移酶-1 (DNMT-1)、辅激活剂相关精氨酸甲基转移酶 (CARM-1) 和神经酰胺酶， 以及酵母选择性 DMA 修复和细胞检查点目标。这些目标也将在 SIO 拥有多种专注于传染病的检测（筛选耐药病原体和 对于两种选定的细菌外排泵的抑制剂）。 - 继续推进先前的发现（Salinosporamide A、卤酰亚胺、马尾藻酰胺 A 和几种 其他分子）用于 BMS P388 和 L1210 白血病以及小鼠实体瘤的体内评估 型号 M109、Mam16/C 和 M50766。