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
- 来源:
- 关键词:Antimetastatic AgentAntineoplastic AgentsBar CodesBiochemicalBiologicalBiological AssayBreast Cancer CellCell LineCellsCharacteristicsChemical WeaponsChemicalsCollectionColorectal CancerCoupledCyanobacteriumCytotoxinDataData SetDevelopmentDimensionsDolastatin 10Drug resistanceEventFloridaFundingFutureG-Protein-Coupled ReceptorsGSTP1 geneGene ClusterGenesGeneticGrowthHCT116 CellsHabitatsHawaiiHistone Deacetylase InhibitorInvestigationKnowledgeLaboratoriesLearningLibrariesMalignant NeoplasmsMalignant neoplasm of pancreasMass Spectrum AnalysisMetagenomicsMicrotubulesModelingMolecularMolecular AnalysisMolecular TargetMorphologyMusNatural Product DrugNatural ProductsNeoplasm MetastasisNuclearOrganismPathway interactionsPatternPeptide HydrolasesPharmaceutical ChemistryPhenotypePhylogenetic AnalysisPlanet EarthReporter GenesResearchRibosomal RNASamplingSourceStructureSynthesis ChemistryTaxonomyTranslatingValidationVascular Endothelial Growth Factorsangiogenesisapratoxincancer cellcancer drug resistancecancer preventioncancer therapycarcinogenesischemical synthesiscolon cancer cell linecytotoxicitydrug discoveryefficacy studyexperiencegenetic informationhypoxia inducible factor 1in vivoinhibitorinnovationmalignant breast neoplasmmarinemilligramnovelnovel anticancer drugnovel therapeuticspreservationprogramsprostate cancer cellrRNA Genesscreeningsecondary metabolitesuccesstooltranscription factortumor xenograft
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
Structural Diversity and Anticancer Activity of Marine-Derived Elastase Inhibitors: Key Features and Mechanisms Mediating the Antimetastatic Effects in Invasive Breast Cancer.
- DOI:10.1002/cbic.201700627
- 发表时间:2018-04-16
- 期刊:
- 影响因子:0
- 作者:Al-Awadhi FH;Paul VJ;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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