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:10436311
- 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 MedicineCollectionComplexComponent 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 HealthUniversitiesValidationYinantagonistbasecancer immunotherapychemical resourcecombatdeep oceandrug candidateeffective therapyexperimental studyfungusimprovedinhibitorinstrumentationlarge scale productionlymphoid neoplasmmarine natural productmelanomameltingmicrobialmicroorganismmilligrammouse modelnovel therapeuticsprofessorprogrammed cell death ligand 1programmed cell death protein 1programsprotein protein interactionresponsescreeningsmall 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.
项目摘要和相关性
项目概要:
这个合作项目的广泛的长期目标是发现小分子
可以替代抗体作为PD-1检查点抑制剂的治疗剂。迄今为止,
分子已经被批准用于该应用,尽管小分子的益处
药物治疗中的生物制剂是显而易见的。该项目利用了一个大型的
收集(多达30 000个样品)结构独特的海洋微生物代谢物,
显示为开发抗癌剂的固体来源。此系列,可用
在斯克里普斯海洋学研究所,加州大学圣地亚哥分校,从博士威廉Fenical将接口
与南京中医药大学的尹璐博士的癌症生物学实验室合作,
使用市售的基于细胞的PD-1生物测定筛选选择性抑制剂
约束力当活性代谢产物被发现时,它们将在各种次级代谢产物中被筛选。
分析以显示选择性结合。最后,验证PD-1结合抑制剂将在
通过大规模培养获得了数毫克的量,并提供给陆博士进行评估,
选择癌症的小鼠和大鼠异种移植模型。
相关性:
该项目旨在通过发现小分子来改善癌症的免疫治疗
选择性结合蛋白PD-1,当结合PDL-1时,负责
免疫系统的失活。用抗体(蛋白质)替代目前的抗体(蛋白质)治疗。
小分子药物有可能提高治疗效果并将明显降低药物成本。
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)
专利数量(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:
10669189 - 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:
10216205 - 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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口服抗肿瘤药物的获取延迟
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- 批准号:
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