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.

这是一个竞争性更新的应用程序，继续探索海洋微生物作为一个新的