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

本任务令（TO15）的重点是在小鼠和/或大鼠的生物样品（血浆和组织）中定量测量(i)来那度胺，（ii）泊马度胺和（iii）与之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具有有效抗炎、免疫调节和抗癌活性的药物。来那度胺和泊马度胺影响的关键生物学靶点包括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-除了这两种主要化合物外，还包括慢性全身性炎症和/或神经炎症等与衰老相关的各种疾病。与这些研究相关的是，需要将药物在临床前动物模型（小鼠和/或大鼠）中的药效学效应与药物在血浆和组织室中的药代动力学联系起来。本任务命令涉及血浆和组织样本中这些物质的定量分析，以支持新的和更有效的药物来减少衰老疾病中的炎症。

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.