Imaging agents for synucleinopathy drug discovery
用于突触核蛋白病药物发现的显像剂
基本信息
- 批准号:9318582
- 负责人:
- 金额:$ 18.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAlzheimer&aposs DiseaseAmino Acid SequenceAmyloidAmyloid beta-ProteinAmyloidosisAppearanceBindingBiochemicalBiological MarkersBiological TestingBrain imagingBrain regionCell physiologyCellsClinical TrialsDementiaDepositionDetectionDevelopmentDiseaseDisease ProgressionDrug KineticsEarly identificationElderlyEvaluationGenerationsGoalsHumanIndividualInvestigational TherapiesLaboratoriesLeadLesionLewy BodiesLewy Body DementiaLewy Body DiseaseLigand BindingMetabolismMethodsMindMusNeuritesNeurodegenerative DisordersNeurofibrillary TanglesNeuronsNeuropil ThreadsParkinson DiseaseParkinson&aposs DementiaPathologyPatientsPerformancePittsburgh Compound-BPlayPositron-Emission TomographyPrevalenceProcessReagentResearchRoleSenile PlaquesSeriesSpatial DistributionSpecimenStaging SystemStilbenesStructureStructure-Activity RelationshipTimeTissuesalpha synucleinbasebenzothiazolebeta pleated sheetbiomarker developmentdisorder subtypedrug discoveryextracellularimaging agentimaging modalityimprovedin vivoinsightpatient populationpatient stratificationpopulation stratificationprotein aggregateradiotracersegregationsmall moleculestemsynucleinopathytau Proteinstau aggregationvalidation studies
项目摘要
Project Summary/Abstract
Drug discovery efforts targeting dementing illnesses of the elderly have been hampered by a series of failed
clinical trials. The negative results could reflect misunderstanding of disease mechanisms, but they also may
stem from study of heterogeneous patient populations with disease that had advanced too far to benefit from
therapy. According to the latter hypothesis, better stratification of patient populations and identification of early
stage disease could greatly improve clinical trial performance. This application seeks to develop small-
molecule probes of α-synuclein aggregates that are found in a range of neurodegenerative disorders including
Lewy Body Disease (LBD), the second leading cause of dementia in the U.S. Radiotracers based on such
compounds could serve to detect pre-mortem disease early in its course, to distinguish forms of
synucleinopathy from pure Alzheimer's disease, and to establish disease stage on the basis of pathology
spatial distribution. To address this need, an iterative discovery approach involving structure activity
relationship analysis is proposed, followed by lead optimization studies. Over the long-term, when combined
with emerging therapies for neurodegenerative disorders, direct pre-mortem detection of protein aggregates
has the potential to improve drug discovery efforts for dementia.
项目摘要/摘要
针对老年人痴呆症的药物发现努力因一系列失败而受阻
临床试验。负面结果可能反映了对疾病机制的误解,但它们也可能
源于对疾病进展太快而无法受益的不同患者群体的研究
心理治疗。根据后一种假设,更好地对患者群体进行分层并识别早期
阶段性疾病可以极大地提高临床试验绩效。此应用程序旨在开发小型-
在一系列神经退行性疾病中发现的α-突触核蛋白聚集体的分子探针,包括
路易体病(LBD)是美国导致痴呆症的第二大原因。
化合物可用于在死亡前疾病的早期发现,区分疾病的形式
从单纯阿尔茨海默病合并核素病出发,在病理基础上建立疾病分期
空间分布。为了满足这一需求,涉及结构活动的迭代发现方法
提出了关系分析,并在此基础上进行了线索优化研究。从长远来看,当两者结合在一起时
随着治疗神经退行性疾病的新疗法的出现,蛋白质聚集体的直接死前检测
有可能改善痴呆症的药物发现工作。
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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Jeff Kuret其他文献
Jeff Kuret的其他文献
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{{ truncateString('Jeff Kuret', 18)}}的其他基金
Imaging agents for synucleinopathy drug discovery
用于突触核蛋白病药物发现的显像剂
- 批准号:
9182629 - 财政年份:2016
- 资助金额:
$ 18.59万 - 项目类别:
STRUCTURE, FUNCTION, AND REGULATION OF CASEIN KINASE-1
酪蛋白激酶-1 的结构、功能和调控
- 批准号:
6386731 - 财政年份:1997
- 资助金额:
$ 18.59万 - 项目类别:
STRUCTURE, FUNCTION, AND REGULATION OF CASEIN KINASE-1
酪蛋白激酶-1 的结构、功能和调控
- 批准号:
6031731 - 财政年份:1997
- 资助金额:
$ 18.59万 - 项目类别:
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