Discovery of PD-1/PDL-1 inhibitors from marine microbial natural products
从海洋微生物天然产物中发现PD-1/PDL-1抑制剂
基本信息
- 批准号:10669189
- 负责人:
- 金额:$ 18.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-14 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AntibodiesAntineoplastic AgentsAquacultureBacteriaBindingBinding ProteinsBiological AssayBiomedical ResearchBuffersCalorimetryCancer BiologyCell LineCell SurvivalCellsChemicalsChinaChinese Hamster Ovary CellChinese Traditional MedicineCollaborationsCollectionComplexComponent of the National Cancer InstituteDevelopmentDimethyl SulfoxideDrug CostsDyesEvaluationFermentationGoalsHumanImmune checkpoint inhibitorImmune systemImmunoprecipitationImmunotherapyIn VitroInstitutionInterferometryKineticsLymphocyteLymphocyte ActivationMalignant NeoplasmsMeasurementMeasuresMelanoma CellModelingMolecularMusNatural ProductsOceanographyOceansPD-1 inhibitorsPD-1/PD-L1Pharmaceutical PreparationsPharmacologyPharmacotherapyPharmacy SchoolsPromegaProteinsProtocols documentationRattusResearch PersonnelResourcesSamplingSolidSourceSpectrometry, Mass, Electrospray IonizationStructureSystemT-Cell ActivationT-LymphocyteTechniquesTestingTimeTitrationsTreatment EfficacyUnited States National Institutes of HealthUniversitiesValidationYinantagonistcancer immunotherapychemical resourcecombatdeep oceandrug candidateeffective therapyexperimental studyfungusimprovedinhibitorinstrumentationlarge scale productionmarinemarine natural productmelanomameltingmicrobialmicroorganismmilligrammouse modelnovel therapeuticsprofessorprogrammed cell death ligand 1programmed cell death protein 1programsresponsescreeningsmall moleculesmall molecule therapeuticstumor growth
项目摘要
Project Summary and Relevance
Project Summary:
The broad, long-term objective of this collaborative project is the discovery of small molecule
therapeutics that can replace antibodies as inhibitors of the PD-1 checkpoint. To date, no small
molecules have been approved for this application, although the benefits of small molecules
over biologicals in drug therapy is clear. This project capitalizes on the existence of a large
collection (up to 30,000 samples) of structurally unique marine microbial metabolites that have
shown to be a solid source for the development of anticancer agents. This collection, available
at the Scripps Institution of Oceanography, UCSD, from Dr. William Fenical will be interfaced
with the cancer biology lab of Dr. Yin Lu at the Nanjing University of Chinese Medicine, to
screen for selective inhibitors using a commercially-available cell-based bioassay for PD-1
binding. When active metabolites are discovered, they will be screened in a variety of secondary
assays to show selective binding. Finally, verified PD-1binding inhibitors will be produced in
multi-milligram amounts by large-scale cultivation and provided to Dr. Lu for evaluation in
mouse and rat xenograph models of select cancers.
Relevance:
This project aims to improve on the immunotherapy of cancer by discovering small molecules
that selectively bind to the protein PD-1, which when bound to PDL-1 is responsible for the
deactivation of the immune system. Replacing the current antibody (protein) therapy with a
small molecule drug is likely to improve treatment efficacy and will clearly reduce drug cost.
项目摘要及相关性
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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William Fenical其他文献
William Fenical的其他文献
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{{ truncateString('William Fenical', 18)}}的其他基金
Discovery of PD-1/PDL-1 inhibitors from marine microbial natural products
从海洋微生物天然产物中发现PD-1/PDL-1抑制剂
- 批准号:
10216205 - 财政年份:2020
- 资助金额:
$ 18.58万 - 项目类别:
Discovery of PD-1/PDL-1 inhibitors from marine microbial natural products
从海洋微生物天然产物中发现PD-1/PDL-1抑制剂
- 批准号:
10436311 - 财政年份:2020
- 资助金额:
$ 18.58万 - 项目类别:
An Accurate Mass TOF Mass Spectrometer - HPLC System for Marine Organic Chemistry
精确质量 TOF 质谱仪 - 用于海洋有机化学的 HPLC 系统
- 批准号:
8246778 - 财政年份:2012
- 资助金额:
$ 18.58万 - 项目类别:
Antitumor-Antibiotics from Marine Microorganisms
来自海洋微生物的抗肿瘤抗生素
- 批准号:
7909499 - 财政年份:2009
- 资助金额:
$ 18.58万 - 项目类别:
The Discovery of New Antibiotics from Deep Sea Actinomycete Bacteria
从深海放线菌中发现新抗生素
- 批准号:
7931427 - 财政年份:2009
- 资助金额:
$ 18.58万 - 项目类别:
The Discovery of New Antibiotics from Deep Sea Actinomycete Bacteria
从深海放线菌中发现新抗生素
- 批准号:
7608702 - 财政年份:2008
- 资助金额:
$ 18.58万 - 项目类别:
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- 批准号:
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