NATURAL PRODUCT DRUGS FROM COLD WATER MARINE ORGANISMS

描述(逐字摘自申请者摘要)：本项目的目标 是追求10个有选择性的主动导联的临床前开发 癌细胞的细胞毒性。160种生物多样性温带植物提取物(320) 和极地海洋大型生物，代表着基本上没有被开发的地区 其他发现计划，在初步研究中进行了评估。活跃分子是 通过对一组癌细胞株的随机筛选确定的 L1210小鼠和CCRF-CEM人白血病细胞生长抑制的比较 与严重药物不敏感肿瘤(小鼠结肠38只，小鼠乳腺410.4只， 人结肠H-116)，并比较对正常干细胞(CFU-GM)的抑制作用 与小鼠和人类实体瘤类型的对比。第一阶段将提纯足够的 使用活动定向分离方法从冻结的原始归档中分离材料 组织，不需要回忆。然后，将在 将描述动物模型及其化学结构。第二阶段将 通过在药物开发流水线中向前推进活性物质来扩大这一努力。 申请人期望具有重要抗癌作用的新化合物 活动将被这个项目发现。主要候选人将是 由白点生物海洋及其合作者通过实体肿瘤开发 动物模型、药代动力学、临床前毒理学及作用机制 研究，届时它们将获得专利并授权给其他人进一步研究 发展。 建议的商业应用：不可用

DESCRIPTION (Verbatim from the applicant's abstract): The goal of this project is to pursue the pre-clinical development of 10 active leads with selective cancer cell cytotoxicity. Extracts (320) of 160 biologically diverse temperate and polar marine macroorganisms, representing regions largely unexplored by other discovery programs, were evaluated in a preliminary study. Actives were determined by random screening against a panel of cancer cell lines that compared growth inhibition of the L1210 murine and CCRF-CEM human leukemias versus severe drug insensitive tumors (murine colon 38, murine mammary 410.4, human colon H-116), and compared inhibition of a normal stem cell (CFU-GM) versus the murine and human solid tumor types. Phase I will purify sufficient material using activity-directed isolation methods from frozen archive raw tissue, no recollection is required. Active leads will then be evaluated in an animal model and their chemical structures will be characterized. Phase II will extend the effort by moving actives forward in the drug-development pipeline. The applicant expects that novel compounds with important anti-cancer activities will be discovered by this project. Lead candidates will be developed by White Point BioMarine and its collaborators through solid-tumor animal models, pharmacokinetics, preclinical toxicology and mechanism of action studies, at which time they will be patented and licensed to others for further development. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE