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: 8485701
• 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/8485701
• 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 Targeting; Elderly; Forskolin; Functional disorder; Generations; Health; 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; 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 cognitive impairment; mouse model; novel; object recognition; phosphodiesterase 4D; phosphoric diester hydrolase; programs; response; scaffold; screening; 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

描述（由申请人提供）：由于美国人口的老龄化，阿尔茨海默病（AD）是一种日益增加的医疗负担。AD是老年人中最常见的痴呆症形式，它影响大脑中对记忆形成和检索至关重要的部分，严重损害一个人独立生活和科普日常活动的能力。与NIH蓝图神经治疗计划合作，我们寻求开发磷酸二酯酶4型（PDE 4）变构调节剂，用于根据以下目标产品简介改善认知。理想情况下，治疗将改善MCI患者的认知并影响AD病理生理学，从而减缓向可能AD的转化。 药物性质最低可接受结果理想结果主要药物适应症改善可能由AD引起的轻度认知障碍（MCI）患者的认知减缓从MCI向可能AD的转化患者人群根据NIAA/AA工作组标准，可能由AD引起的MCI患者根据NIAA/AA工作组标准，可能由AD引起的MCI患者给药方式口服口服治疗持续时间慢性慢性方案口服，每日一次口服，每日一次