ANTICANCER LEADS FROM MARINE MACROORGANISMS AND THEIR ASSOCIATED MICROORGANISMS

海洋微生物及其相关微生物的抗癌作用

基本信息

  • 批准号:
    6237147
  • 负责人:
  • 金额:
    $ 8.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1997
  • 资助国家:
    美国
  • 起止时间:
    1997-09-30 至 1998-08-31
  • 项目状态:
    已结题

项目摘要

While effective therapeutic agents for the treatment of leukemias and lymphomas are available, little progress has been made in the development of new drugs that are useful for the treatment of clinically important tumors, such as breast, colon, lung, ovarian, and prostate. The lack of success in this area can be traced to the absence of effective assay models or screening technologies for the discovery of such agents. However, recent advances in our knowledge of cancer biology have catalyzed the development of innovative new methods.for the detection of compounds that affect biochemical targets such as oncogene products, tumor suppressor gene products, proteins involved in various signal transduction pathways, and proteins involved in apoptosis. We believe that compounds which have a mechanism of action involving one of these areas will be active against the important solid tumors listed above. To fully exploit the arsenal of new screens provided by Sandoz Pharmaceuticals, we will endeavor to provide compounds and extracts resulting from the widest possible diversity of biosynthetic pathways. Therefore, we will not only investigate marine sponges and ascidians, which are well proven sources of an array of unique secondary metabolites, we will also access the microbial fauna (i.e., bacteria and actinomycetes) present on the surfaces or within the tissues of these invertebrates. In this way we will maximize our resources and utilize the research specimens to their fullest potential. The overall goal of this segment of the NCNPDDG proposal is the discovery of new compounds produce by marine invertebrates, particularly sponges and ascidians, or their-associated microorganisms that will serve as new anticancer chemotherapeutic leads. To succeed in satisfying this goal, we propose to do the following: (a) obtain marine sponges and ascidians to serve both as a pool of biologically active compounds as well as a unique nutrient-rich source of microorganisms; (b) culture marine bacteria and actinomycetes from the surfaces and interior spaces of the collected invertebrates; (c) employ mechanism-based assays to uncover extracts containing new chemical agents which act on important biochemical targets; (d) optimize fermentation conditions for those marine isolates which produce active metabolites; (e) efficiently isolate active metabolites, guided by rapid primary biochemical assays; (f) elucidate the chemical structures of active compounds using spectrochemical methods; (g) initiate recollection or scale-up fermentation and re-isolation of those compounds selected for further pharmacological study or preclinical investigation; (h) prepare semi- synthetic analogs of active compounds for investigation of structure- activity relationships; and (i) obtain patent coverage for promising antitumor natural products and their derivatives.
尽管用于治疗白血病和白血病的有效治疗剂 淋巴瘤是可用的,几乎没有进展,在发展 用于治疗临床上重要的 肿瘤,如乳腺癌、结肠癌、肺癌、卵巢癌和前列腺癌。缺乏 这一领域的成功可以追溯到缺乏有效的分析 用于发现此类代理的模型或筛选技术。 然而,我们对癌症生物学知识的最新进展 促进了创新新方法的发展。 影响生物化学靶标如致癌基因产物的化合物, 肿瘤抑制基因产物,参与各种信号传导的蛋白质 转导途径和参与细胞凋亡的蛋白质。我们认为 这些化合物的作用机制包括 这些区域将对上述重要的实体瘤具有活性。 为了充分利用山德士提供的新屏幕库, 制药,我们将奋进提供化合物和提取物, 这是由于生物合成途径的多样性。 因此,我们不仅要研究海绵和海鞘, 这是一系列独特的二次能源的来源, 代谢物,我们还将访问微生物动物群(即,细菌和 放线菌)存在于这些表面或组织内 无脊椎动物这样,我们将最大限度地利用我们的资源, 充分发挥它们的潜力来研究标本 NCNPDDG提案这一部分的总体目标是发现 海洋无脊椎动物,特别是海绵, 和海鞘,或其相关的微生物,将作为新的 抗癌化疗药物。为了实现这一目标, 我们建议采取以下行动:(a)获取海绵和海鞘 既作为生物活性化合物的库,又作为 独特的营养丰富的微生物来源;(B)培养海洋生物 细菌和放线菌从表面和内部空间的 收集的无脊椎动物;(c)采用基于机制的分析, 含有新化学试剂的提取物, 生物化学目标;(d)优化发酵条件, 产生活性代谢物的海洋分离物;(e)有效分离 活性代谢物,以快速初级生物化学分析为指导;(f) 阐明活性化合物的化学结构, 光谱化学方法;(g)开始重新收集或按比例放大 发酵和再分离那些选择用于进一步 药理学研究或临床前研究;(h)制备半- 用于研究结构的活性化合物的合成类似物- (一)专利权的授予;(二)专利权的授予; 抗肿瘤天然产物及其衍生物。

项目成果

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BRADLEY S DAVIDSON其他文献

BRADLEY S DAVIDSON的其他文献

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{{ truncateString('BRADLEY S DAVIDSON', 18)}}的其他基金

NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
来自海洋生物的新型抗微管剂
  • 批准号:
    6665809
  • 财政年份:
    2002
  • 资助金额:
    $ 8.08万
  • 项目类别:
NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
来自海洋生物的新型抗微管剂
  • 批准号:
    6486689
  • 财政年份:
    2001
  • 资助金额:
    $ 8.08万
  • 项目类别:
NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
来自海洋生物的新型抗微管剂
  • 批准号:
    6336759
  • 财政年份:
    2000
  • 资助金额:
    $ 8.08万
  • 项目类别:
NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
来自海洋生物的新型抗微管剂
  • 批准号:
    2839719
  • 财政年份:
    1999
  • 资助金额:
    $ 8.08万
  • 项目类别:
ANTICANCER LEADS FROM MARINE MACROORGANISMS AND THEIR ASSOCIATED MICROORGANISMS
海洋微生物及其相关微生物的抗癌作用
  • 批准号:
    6203188
  • 财政年份:
    1999
  • 资助金额:
    $ 8.08万
  • 项目类别:
NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
来自海洋生物的新型抗微管剂
  • 批准号:
    6377146
  • 财政年份:
    1999
  • 资助金额:
    $ 8.08万
  • 项目类别:
NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
来自海洋生物的新型抗微管剂
  • 批准号:
    6173871
  • 财政年份:
    1999
  • 资助金额:
    $ 8.08万
  • 项目类别:
ANTICANCER LEADS FROM MARINE MACROORGANISMS AND THEIR ASSOCIATED MICROORGANISMS
海洋微生物及其相关微生物的抗癌作用
  • 批准号:
    6102635
  • 财政年份:
    1998
  • 资助金额:
    $ 8.08万
  • 项目类别:
ANTINEOPLASTIC AGENTS FROM MARINE BACTERIA
来自海洋细菌的抗肿瘤剂
  • 批准号:
    6249627
  • 财政年份:
    1997
  • 资助金额:
    $ 8.08万
  • 项目类别:
ANTINEOPLASTIC AGENTS FROM MARINE BACTERIA
来自海洋细菌的抗肿瘤剂
  • 批准号:
    3460531
  • 财政年份:
    1992
  • 资助金额:
    $ 8.08万
  • 项目类别:

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