THE SYNTHESIS AND PRECLINICAL STUDIES OF NEW TREATMENTS FOR NEURODEGENERATIVE DISEASE, DIABETES MELLITUS, CONGESTIVE HEART FAILURE, ONCOLOGIC AND IMMUNOLOGIC DISEASES

神经退行性疾病、糖尿病、充血性心力衰竭、肿瘤和免疫疾病新疗法的综合和临床前研究

• 批准号: 8930677
• 负责人: CAROL E GREEN
• 金额: $ 10.06万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-14 至 2016-01-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8930677
• 关键词: Aging; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Biological; Chronic; Congestive Heart Failure; Diabetes Mellitus; Disease; Drug Kinetics; Immune System Diseases; Inflammation; Interleukin-6; Malignant Neoplasms; Measurement; Mus; NF-kappa B; Neurodegenerative Disorders; Pharmaceutical Preparations; Pharmacodynamics; Plasma; Rattus; Sampling; Tissue Sample; Tissues; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factors; analog; design; human TNF protein; lenalidomide; neuroinflammation; novel; pre-clinical; preclinical study

The focus of this Task Order (TO15) is the quantitative measurement of (i) lenalidomide, (ii) pomalidomide and (iii) four novel analogues associated with these (designed and synthesized within IRP, NIA) - in biological samples (plasma and tissue) of mice and or rats. Lenalidomide and pomalidomide are clinically approved drugs that possess potent anti-inflammatory, immunomodulatory and anti-cancer activity. Key biological targets that lenalidomide and pomalidomide impact include TNF-alpha, IL-6, VEGF and NF-kB. The IRP, NIA is synthesizing and evaluating novel analogues of lenalidomide and pomalidomide – in addition to both primary compounds in a variety of disorders associated with aging that involve either chronic systemic inflammation and/or neuroinflammation. Related with these studies, there is a requirement to associate pharmacodynamic effects of drugs in preclinical animal models (mice and/or rats) with pharmacokinetics of the agents in plasma and tissue compartments. This Task order relates to quantitative analysis of these agents in plasma and tissue samples - in support of new and more effective drugs to reduce inflammation in diseases of aging.

该任务指令 (TO15) 的重点是定量测量小鼠和/或大鼠生物样品（血浆和组织）中的 (i) 来那度胺、(ii) 泊马度胺和 (iii) 与这些相关的四种新型类似物（在 IRP、NIA 内设计和合成）。来那度胺和泊马度胺是临床批准的药物，具有有效的抗炎、免疫调节和抗癌活性。来那度胺和泊马度胺影响的关键生物靶标包括 TNF-α、IL-6、VEGF 和 NF-kB。 IRP、NIA 正在合成和评估来那度胺和泊马度胺的新型类似物，以及这两种主要化合物用于治疗多种与衰老相关的慢性全身炎症和/或神经炎症疾病。与这些研究相关，需要将药物在临床前动物模型（小鼠和/或大鼠）中的药效学作用与药物在血浆和组织区室中的药代动力学联系起来。该任务指令涉及对血浆和组织样本中这些药物的定量分析，以支持新的、更有效的药物来减少衰老疾病中的炎症。