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

Sri International, Menlo Park CA

Investigators

Abstract

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.