HTS to Identify Inhibitors of c-Abl kinase for the Potential Treatment of Alzheimer's Disease

National Center For Advancing Translational Sciences

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Abstract

The NCATS Early Translation Branch (ETB) hosts a broad and comprehensive program for the discovery of drug candidates directed towards rare diseases and pharmacological tools to probe the function of the human genome. ETB conducts research to understand the underlying principles driving the translation of basic research discoveries into tangible improvements in human health. During this period, the project team completed the structure activity relationship studies producing a highly potent selective cAbl allosteric inhibitor with good pharmacokinetics and preferential distribution toward CNS. Evaluation of this inhibitor in several mouse models of Alzheimer's disease results in good efficacy, with recovery of cognitive impairments and reduction of plaque and inflammatory markers.