Production and quality analysis of clinical drug for a novel CNS protein kinase inhibitor therapeutic candidate
新型中枢神经系统蛋白激酶抑制剂治疗候选药物的生产和临床质量分析
基本信息
- 批准号:9902252
- 负责人:
- 金额:$ 201.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2021-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmyloidAnimal ModelArtsAttenuatedCanis familiarisCentral Nervous System DiseasesClinicalClinical ResearchClinical TrialsCognition DisordersComplexDevelopmentDiseaseDisease ProgressionDrug TargetingDrug effect disorderFoundationsFrontotemporal DementiaFunctional disorderFundingGMP lotsGelatinGenerationsGoalsHeat shock proteinsImpaired cognitionInvestigationInvestigational DrugsNeurodegenerative DisordersNeurogliaNeuronsOutcomeParkinson DiseasePathway interactionsPatientsPharmaceutical PreparationsPharmacologyPhasePhase II Clinical TrialsPreparationProductionProgressive DiseaseProtein IsoformsProtein-Serine-Threonine KinasesRattusSchemeSpecificityStressSynapsesTestingTherapeuticToxicologyTreatment EfficacyValidationWorkcapsuleclinical developmentdrug candidatedrug productiondrug qualityfirst-in-humanimprovedinsightlarge scale productionlot productionneglectneuroinflammationnovelnovel therapeutic interventionpreventprotein kinase inhibitortherapeutic candidatetherapeutic developmentvirtual
项目摘要
ABSTRACT
Alzheimer’s disease (AD) and related dementias are increasing rapidly yet, remarkably, there are no approved
disease modifying drugs. Virtually all trials targeting amyloid related pathways have failed over the last 10
years. Regrettably, few alternative targets or pathways have been explored. Therefore, there is an urgent need
to explore alternative pathways as monotherapies or as constituents of a multi-drug armamentarium for a
complex disease. An alternative view of progressive neurodegenerative disorders such as AD, frontotemporal
dementia, and Parkinson’s disease is diseases of progressive synaptic dysfunction. Protein kinase inhibitors
(PKI) are logical candidates to explore as potential attenuators of such progressive synaptic dysfunction and
cognitive decline. However, PKI drug candidates are under explored as a foundation for CNS disease-
modifying therapeutic development and there are currently no approved CNS PKI drugs for any indication. This
proposal is a discrete component of a clinical development campaign for a novel stress PKI drug candidate,
MW01-18-150SRM (= MW150) that represents a paradigm change for CNS targeted diseases such as AD.
MW150 is distinct from past or current drug candidates in AD clinical trials. MW150 ameliorates cognitive
dysfunction in discrete AD-relevant animal models. MW150 has a unique profile of target recognition,
pharmacological features, and efficacy outcomes. A GMP production scheme was developed and provided the
first released clinical drug supply for first-in-human (FIH) trials. This prior art provides a firm foundation for a
commercial scale production of GMP drug substance (API) and drug product (drug-in-capsule). There is an
immediate need for multi-Kg scale production of drug substance and validation of commercial drug product in
order to move into first-in-patient (FIP) status without untoward delays. In this regard, our specific aims are:
aim 1, develop and validate a large-scale production lot for GMP clinical drug substance (API); aim 2, generate
a pilot lot of. Completion of aim 1 is required immediately for the extended toxicology studies. Completion of
aims 1 and 2 allows immediate generation of the phase 2 IND quality (CMC) section and initiation of planning
for phase 2 FIP trials. The FIP trials will provide alternative therapeutic approaches to AD and related
dementia. The clinical campaign is directly testing the hypothesis that an isoform selective PKI drug can
address the synaptic dysfunction and injurious neuroinflammation that characterize diverse neurodegenerative
diseases. Further, attenuating the disease relevant pathways associated with increased p38aMAPK activity in
both neurons and glia tests the hypothesis that improved efficacy can be obtained with a single target drug that
works via pleiotropic drug action.
摘要
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Daniel Martin Watterson其他文献
Daniel Martin Watterson的其他文献
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{{ truncateString('Daniel Martin Watterson', 18)}}的其他基金
Preclinical Alzheimers Disease Drug Development of Novel MAPK Inhibitors
新型 MAPK 抑制剂的临床前阿尔茨海默病药物开发
- 批准号:
8422736 - 财政年份:2012
- 资助金额:
$ 201.87万 - 项目类别:
Preclinical Alzheimers Disease Drug Development of Novel MAPK Inhibitors
新型 MAPK 抑制剂的临床前阿尔茨海默病药物开发
- 批准号:
8724322 - 财政年份:2012
- 资助金额:
$ 201.87万 - 项目类别:
Preclinical Alzheimers Disease Drug Development of Novel MAPK Inhibitors
新型 MAPK 抑制剂的临床前阿尔茨海默病药物开发
- 批准号:
8549070 - 财政年份:2012
- 资助金额:
$ 201.87万 - 项目类别:
Preclinical Alzheimers Disease Drug Development of Novel MAPK Inhibitors
新型 MAPK 抑制剂的临床前阿尔茨海默病药物开发
- 批准号:
8852032 - 财政年份:2012
- 资助金额:
$ 201.87万 - 项目类别:
Preclinical Alzheimers Disease Drug Development of Novel MAPK Inhibitors
新型 MAPK 抑制剂的临床前阿尔茨海默病药物开发
- 批准号:
9101921 - 财政年份:2012
- 资助金额:
$ 201.87万 - 项目类别:
Development of Novel p38 MAPK Inhibitors as Therapeutics for CNS Disorders
开发新型 p38 MAPK 抑制剂作为中枢神经系统疾病的治疗药物
- 批准号:
8067063 - 财政年份:2008
- 资助金额:
$ 201.87万 - 项目类别:
Development of Novel p38 MAPK Inhibitors as Therapeutics for CNS Disorders
开发新型 p38 MAPK 抑制剂作为中枢神经系统疾病的治疗药物
- 批准号:
7663102 - 财政年份:2008
- 资助金额:
$ 201.87万 - 项目类别:
Integrative Chemical Biology of Neurodegeneration: Foundation to Novel Therapies
神经退行性变的综合化学生物学:新疗法的基础
- 批准号:
7575625 - 财政年份:2008
- 资助金额:
$ 201.87万 - 项目类别:
Development of Novel p38 MAPK Inhibitors as Therapeutics for CNS Disorders
开发新型 p38 MAPK 抑制剂作为中枢神经系统疾病的治疗药物
- 批准号:
8286256 - 财政年份:2008
- 资助金额:
$ 201.87万 - 项目类别:
Development of Novel p38 MAPK Inhibitors as Therapeutics for CNS Disorders
开发新型 p38 MAPK 抑制剂作为中枢神经系统疾病的治疗药物
- 批准号:
7849671 - 财政年份:2008
- 资助金额:
$ 201.87万 - 项目类别:














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