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Optimization of microtubule-stabilizing triazolopyrimidines as therapeutics for Alzheimer's disease and related tauopathies

Optimization of microtubule-stabilizing triazolopyrimidines as therapeutics for Alzheimer's disease and related tauopathies
优化微管稳定三唑并嘧啶作为阿尔茨海默病和相关 tau蛋白病的治疗方法
批准号：
10553899
负责人：
KURT R. BRUNDEN
金额：
$31.15万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
项目状态：
已结题
起止时间：
2019-03-01 至 2024-02-29
来源：
https://reporter.nih.gov/project-details/10553899
关键词：
AcuteAdverse effectsAlzheimer&aposs disease therapeuticBiological AssayDoseDrug KineticsIntravenousLaboratoriesMaximum Tolerated DoseMicrotubule StabilizationNeuronsOralPharmacodynamicsProdrugsTauopathiesTestingWild Type MouseWork

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英文摘要
Statement of Work Specific activities overseen by the Brunden laboratory include: 1) testing of prodrugs in established HEK293 and neuron microtubule stabilization assays; 2) intravenous and oral pharmacokinetic testing of prodrugs to determine the rate of conversion of prodrugs to the desired active compound; 3) assessment of preferred prodrugs for pharmacodynamic effect in wild-type mice to establish the minimum effective dose and duration of compound effect; and 4) determination of preferred prodrug acute maximum tolerated dose and the no adverse effect dose after 3 weeks of dosing.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Microtubule-Stabilizing 1,2,4-Triazolo[1,5-a]pyrimidines as Candidate Therapeutics for Neurodegenerative Disease: Matched Molecular Pair Analyses and Computational Studies Reveal New Structure-Activity Insights.
DOI： 10.1021/acs.jmedchem.2c01411
发表时间： 2023-01-12
期刊： JOURNAL OF MEDICINAL CHEMISTRY
影响因子： 7.3
作者： [Alle, Thibault, Varricchio, Carmine, Yao, Yuemang, Lucero, Bobby, Nzou, Goodwell, Demuro, Stefania, Muench, Megan, Vuong, Khoa D., Oukoloff, Killian, Cornec, Anne-Sophie, Francisco, Karol R., Caffrey, Conor R., Lee, Virginia M. -Y., Smith III, Amos B., Brancale, Andrea, Brunden, Kurt R., Ballatore, Carlo]
通讯作者： Ballatore, Carlo
Optimization of microtubule-stabilizing triazolopyrimidines as therapeutics for Alzheimer's disease and related tauopathies
  • 批准号：
    10364719
  • 项目类别：
  • 资助金额：
    $74.61万
  • 财政年份：
    2019
  • 负责人：
    KURT R. BRUNDEN
  • 依托单位：
    UNIVERSITY OF PENNSYLVANIA
Optimization of microtubule-stabilizing triazolopyrimidines as therapeutics for Alzheimer's disease and related tauopathies
  • 批准号：
    10398425
  • 项目类别：
  • 资助金额：
    $15.99万
  • 财政年份：
    2019
  • 负责人：
    KURT R. BRUNDEN
  • 依托单位：
    UNIVERSITY OF PENNSYLVANIA
Orally-absorbed, small molecule microtubule-stabilizers for tauopathy treatment
  • 批准号：
    8478876
  • 项目类别：
  • 资助金额：
    $47.86万
  • 财政年份：
    2013
  • 负责人：
    KURT R. BRUNDEN
  • 依托单位：
    UNIVERSITY OF PENNSYLVANIA
Orally-absorbed, small molecule microtubule-stabilizers for tauopathy treatment
  • 批准号：
    8670685
  • 项目类别：
  • 资助金额：
    $47.86万
  • 财政年份：
    2013
  • 负责人：
    KURT R. BRUNDEN
  • 依托单位：
    UNIVERSITY OF PENNSYLVANIA
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