Novel Targeted Anticancer Agents from Marine Cyanobacteria

来自海洋蓝藻的新型靶向抗癌剂

基本信息

  • 批准号:
    10738315
  • 负责人:
  • 金额:
    $ 4.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-03-06 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Cyanobacteria are among the most ancient organisms on Earth and have evolved chemical weapons for defensive purposes, which we are exploiting for anticancer drug discovery. Our past research has exemplified that marine cyanobacteria produce compounds with exceptionally potent activity and/or possess unusual or first- in-class inhibitors with novel mechanisms of action. We apply a broad yet focused screening platform to maximize discovery rate of new anticancer agents. We also integrate a synthetic chemistry component into our program in order to perform rigorous biological studies to rapidly add value to our discoveries and to help solve the supply problem. Specifically, we will carry out field collections of marine cyanobacteria and prepare fraction libraries for screening in a set of innovative pathway-focused cell-based assays, utilizing various isogenic colorectal cancer cell lines and reporter gene assays, as well as newly developed unbiased phenotypic assays. We will perform dereplication, identify cyanobacteria through molecular analysis and establish phylogenetic relationships among benthic cyanobacteria. Samples will be prioritized based on bioactivity profiles and genetic uniqueness for further processing. Prioritized samples will be subjected to bioassay-guided isolation of the active compounds. Structures will be determined using NMR and mass spectrometry. Basic validation of bioactivity and secondary assays will be performed before prioritizing targets for further investigation. Selected compounds with intriguing structure and promising validated bioactivity will be targeted for total synthesis so that a rigorous biological characterization can be performed to pinpoint the molecular changes induced in the cancer cell and to determine potential direct targets. For novel noncytotoxic compounds that show potential antimetastatic activity, we will apply an orthogonal target-based screening platform.
项目总结

项目成果

期刊论文数量(71)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria.
  • DOI:
    10.1002/chem.201600674
  • 发表时间:
    2016-06-06
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Gunasekera SP;Li Y;Ratnayake R;Luo D;Lo J;Reibenspies JH;Xu Z;Clare-Salzler MJ;Ye T;Paul VJ;Luesch H
  • 通讯作者:
    Luesch H
A Complementary Chemical and Genomic Screening Approach for Druggable Targets in the Nrf2 Pathway and Small Molecule Inhibitors to Overcome Cancer Cell Drug Resistance.
  • DOI:
    10.1021/acschembio.7b01025
  • 发表时间:
    2018-05-18
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Matthews JH;Liang X;Paul VJ;Luesch H
  • 通讯作者:
    Luesch H
Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium.
  • DOI:
    10.1021/acs.jnatprod.5b00293
  • 发表时间:
    2015-08-28
  • 期刊:
  • 影响因子:
    5.1
  • 作者:
    Salvador-Reyes LA;Sneed J;Paul VJ;Luesch H
  • 通讯作者:
    Luesch H
Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model.
  • DOI:
    10.1007/s10637-018-0647-0
  • 发表时间:
    2019-04
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Cai W;Ratnayake R;Gerber MH;Chen QY;Yu Y;Derendorf H;Trevino JG;Luesch H
  • 通讯作者:
    Luesch H
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HENDRIK LUESCH其他文献

HENDRIK LUESCH的其他文献

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{{ truncateString('HENDRIK LUESCH', 18)}}的其他基金

Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    10005117
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    10693140
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    10524080
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    8633022
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    9025471
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    10380941
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    10477035
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    10246927
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    9241971
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:
Novel Targeted Anticancer Agents from Marine Cyanobacteria
来自海洋蓝藻的新型靶向抗癌剂
  • 批准号:
    8418957
  • 财政年份:
    2013
  • 资助金额:
    $ 4.43万
  • 项目类别:

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Delays in Acquisition of Oral Antineoplastic Agents
口服抗肿瘤药物的获取延迟
  • 批准号:
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  • 财政年份:
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  • 资助金额:
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    2016
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  • 批准号:
    19591274
  • 财政年份:
    2007
  • 资助金额:
    $ 4.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
PNET EXPERIMENTAL THERAPEUTICS--ANTINEOPLASTIC AGENTS AND TREATMENT DELIVERY
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  • 批准号:
    6346309
  • 财政年份:
    2000
  • 资助金额:
    $ 4.43万
  • 项目类别:
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    1999
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  • 财政年份:
    1999
  • 资助金额:
    $ 4.43万
  • 项目类别:
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抗肿瘤药物药理学培训
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    7101017
  • 财政年份:
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抗肿瘤药物药理学培训
  • 批准号:
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  • 批准号:
    2885074
  • 财政年份:
    1999
  • 资助金额:
    $ 4.43万
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    6174221
  • 财政年份:
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