The goal of this proposal is to develop a c-jun-N-terminal kinase 3 (JNK3) isoform selective inhibitor that willenable a regulatory filing for an investigational new drug (IND) to be used in the treatment of Alzheimer'sdisease (AD). A JNK3 isoform selective inhibitor provides a novel mechanism for the treatment of ADcombining benefit for decreasing A production, lowering ER stress and improving cognition, and may havesafety benefits in other tissues because JNK3 expression is limited to the brain and heart. Successfulcompletion of this research will yield novel, innovative JNK3 isoform selective inhibitors for assessment ofclinical efficacy in the treatment of Alzheimer's disease.