PDE4D Allosteric Modulators for Treating Cognitive Impairment

用于治疗认知障碍的 PDE4D 变构调节剂

• 批准号: 8278774
• 负责人: Mark E Gurney
• 金额: $ 23.54万
• 依托单位: TETRA DISCOVERY PARTNERS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278774
• 关键词: 2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole; Active Sites; Affect; Alzheimer' s Disease; Anesthesia procedures; Binding; Biochemical; Biological Assay; Biological Availability; Boxing; Brain; Brain Part; Buffers; Cells; Cellular Assay; Central Nervous System Diseases; Chemosensitization; Clinical; Clinical Trials; Clinical dementia rating scale; Cognition; Cognitive; Collaborations; Crystallization; Cyclic AMP; Cytochrome P450; Dementia; Demographic Aging; Dendritic Spines; Developed Countries; Dose; Drug Delivery Systems; Elderly; Forskolin; Functional disorder; Generations; Hepatocyte; Human; Humulus; Impaired cognition; In Vitro; Inhibitory Concentration 50; Ketamine; Kinetics; Knowledge; Lead; Life; Medical; Memory; Mental Depression; Metabolic Activation; Metabolism; Modeling; Monkeys; Mus; Oral; Pathology; Patients; Persons; Pharmaceutical Preparations; Phase; Plasma; Population; Property; Publishing; Retrieval; Rodent; Rolipram; Safety; Screening procedure; Solubility; Structure; Sum; System; Testing; Therapeutic; Toxic effect; United States National Institutes of Health; Vomiting; Xylazine; base; cognitive function; coping; design; experience; genotoxicity; improved; in vivo; indexing; inhibitor/antagonist; member; mild neurocognitive impairment; mouse model; novel; object recognition; phosphodiesterase 4D; phosphoric diester hydrolase; programs; response; scaffold; synaptic function; working group

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is an increasing medical burden due to the aging demographics of the US population. The most common form of dementia among older adults, AD affects parts of the brain important for memory formation and retrieval, seriously impairing a person's ability to live independently and cope with daily activities. In collaboration with the NIH Blueprint Neurotherapeutics Program, we seek to develop phosphodiesterase Type 4 (PDE4) allosteric modulators for improving cognition in accordance with the Target Product Profile below. Ideally, the therapeutic will improve cognition in MCI patients and impact AD pathophysiology, thereby slowing conversion to probable AD. Drug PropertiesMinimum Acceptable ResultIdeal ResultPrimary Drug IndicationImprovement of cognition in persons with Mild Cognitive Impairment (MCI) due to probable ADSlowing of conversion from MCI to probable ADPatient PopulationPatients with MCI due to probable AD according to the NIAA/AA working group criteriaPatients with MCI due to probable AD according to the NIAA/AA working group criteriaDelivery ModeOralOralTreatment DurationChronicChronicRegimenOral, once dailyOral, once daily PUBLIC HEALTH RELEVANCE: With a growing elderly population in industrialized nations world-wide, drugs to treat Alzheimer's disease (AD) are a critical unmet medical need. We are seeking to develop a new treatment for AD based on allosteric modulation of phosphodiesterase 4D (PDE4D). Ideally, the treatment will reverse or stabilize cognitive decline due to AD.

描述（由申请人提供）：由于美国人口的人口统计，阿尔茨海默氏病（AD）是增加的医疗负担。 AD是老年人中最常见的痴呆症形式，影响大脑的一部分对于记忆形成和检索很重要，严重损害了一个人独立生活和应对日常活动的能力。通过与NIH蓝图神经疗法计划合作，我们寻求开发磷酸二酯酶4型（PDE4）变构调节剂，以根据下面的目标产品概况提高认知。理想情况下，治疗性将改善MCI患者的认知并影响AD病理生理学，从而减慢转化为可能的AD。 药物特性最少可接受的结果导致药物指示对患有轻度认知障碍的人（MCI）认知（MCI）的认知证明，这是由于MCI转化到可能是根据NIAA/AA工作组的ARA AA AA AA AA AA AA的可能ADA，可能会导致MCI转化为可能与MCI的适应性种群患者相关的ADA，因此可能会导致MCI的适应性种群患者。每天每天一次，一次性的chronicchronicchronicronicregimenoral，每天一次 公共卫生相关性：随着全球工业化国家的老年人口的增长，治疗阿尔茨海默氏病（AD）的药物是至关重要的未满足医疗需求。我们正在寻求基于磷酸二酯酶4D（PDE4D）的变构调节来开发AD的新方法。理想情况下，治疗将逆转或稳定由于AD引起的认知能力下降。