Enolase inhibitors as therapeutic leads for Naegleria fowleri infections
烯醇酶抑制剂作为福氏耐格里阿米巴感染的治疗先导药物
基本信息
- 批准号:10739388
- 负责人:
- 金额:$ 20.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-05 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:Amoeba genusAnimalsBiochemicalBiological AssayBody Weight decreasedCellsChemicalsCollectionContinuous InfusionDevelopmentDisease modelDrug DesignEngineeringEnzyme InhibitionEnzymesExperimental Animal ModelGeneticGlioblastomaGoalsHumanHuman Cell LineImmuneImmune responseImmune systemIn VitroInfectionLeadMammalsMedicineMetabolicMetabolismMonitorNaegleriaNaegleria fowleriOutcomeParasitesParentsPathogenicityPathologicPathway interactionsPhosphonic AcidsProbabilityProtein IsoformsProteinsProteomeReagentRodent DiseasesRodent ModelRoleSeriesSpecificityStructureTestingTherapeuticTimeTissuesToxic effectWorkanalogcellular targetingenolaseexperimental studyglucose metabolismimprovedin vivoinflammatory markerinhibitorinsightmortalitymouse modelneoplastic cellnonhuman primatenovelnovel therapeuticspharmacokinetics and pharmacodynamicsphosphonateprimary amebic meningoencephalitistargeted agenttargeted treatmenttherapeutic developmenttherapeutic targettooltreatment response
项目摘要
Project Summary
Human infection by the pathogenic free-living amoeba Naegleria fowleri causes primary
amebic meningoencephalitis (PAM), which in the majority (>95%) of infections end in
fatality. We have recently found that a group of phosphonate inhibitors of the glycolytic
enzyme enolase (ENO) that are well-tolerated in mammals are potent anti-amebic
compounds. The goal of this proposal is to test the hypothesis that the amoeba ENO
(NfENO) is a promising target for therapeutic development and to optimize phosphonate
inhibtors to early lead stage. As part of this, we will use a small collection of inhibitors and a
series of orthologous assays to biochemically validate NfENO as target of the agents and
will determine the effect of the inhibitors on amoebae infections in a rodent disease model,
scoring the immune response to treatment as part of the effort.
项目摘要
人感染致病的自由生活阿米巴鸡奈格勒原虫引起
阿米巴脑膜脑炎(PAM),在大多数(>;95%)感染中以
致命性。我们最近发现了一组磷酸盐类的糖酵解抑制剂
在哺乳动物中耐受性良好的酶烯醇化酶(ENO)是一种有效的抗阿米巴
化合物。这项提议的目标是检验阿米巴ENO的假设
(NfENO)是治疗开发和优化磷酸盐的一个有前途的目标
抑制物进入早期铅阶段。作为这项工作的一部分,我们将使用一小部分抑制剂和
一系列生化验证NfENO作为制剂和靶标的同源分析
将在啮齿动物疾病模型中确定抑制剂对阿米巴感染的影响,
作为努力的一部分,对治疗的免疫反应进行评分。
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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JAMES Culvin MORRIS其他文献
JAMES Culvin MORRIS的其他文献
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{{ truncateString('JAMES Culvin MORRIS', 18)}}的其他基金
Approaches for genetic manipulation of Naegleria fowleri
福氏耐格里虫的基因操作方法
- 批准号:
10641130 - 财政年份:2023
- 资助金额:
$ 20.54万 - 项目类别:
COBRE: Eukaryotic Pathogens Innovation Center (EPIC)
COBRE:真核病原体创新中心(EPIC)
- 批准号:
10494462 - 财政年份:2022
- 资助金额:
$ 20.54万 - 项目类别:
COBRE: Eukaryotic Pathogens Innovation Center (EPIC)
COBRE:真核病原体创新中心(EPIC)
- 批准号:
10666653 - 财政年份:2022
- 资助金额:
$ 20.54万 - 项目类别:
Acquisition of the Agilent Cytation C10 confocal imaging reader for enhancing biomedical research excellence at Clemson University
采购 Agilent Cytation C10 共焦成像阅读器,以提高克莱姆森大学的生物医学研究卓越性
- 批准号:
10798537 - 财政年份:2022
- 资助金额:
$ 20.54万 - 项目类别:
Nutrient sensing and hexokinases in T. brucei
T. brucei 中的营养感应和己糖激酶
- 批准号:
7911534 - 财政年份:2009
- 资助金额:
$ 20.54万 - 项目类别:
Nutrient sensing and hexokinases in T. brucei
T. brucei 中的营养感应和己糖激酶
- 批准号:
7454845 - 财政年份:2008
- 资助金额:
$ 20.54万 - 项目类别:
Identification of Inhibitors of Trypanosoma Brucei Hexokinases
布氏锥虫己糖激酶抑制剂的鉴定
- 批准号:
7459260 - 财政年份:2007
- 资助金额:
$ 20.54万 - 项目类别:
Glucose Sensing and Hexokinases in the African Trypanosome
非洲锥虫中的葡萄糖传感和己糖激酶
- 批准号:
9900822 - 财政年份:
- 资助金额:
$ 20.54万 - 项目类别:
Glucose Sensing and Hexokinases in the African Trypanosome
非洲锥虫中的葡萄糖传感和己糖激酶
- 批准号:
9261578 - 财政年份:
- 资助金额:
$ 20.54万 - 项目类别:
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