Discovery of ZJCK-6-46: A Potent, Selective, and Orally Available Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor for the Treatment of Alzheimer’s Disease
Huanhua Chen,
Xudong Gao,
Xinzhu Li
et al.
Abstract:Targeting dual-specificity tyrosine phosphorylationregulated kinase 1A (DYRK1A) has been verified to regulate the progression of tau pathology as a promising treatment for Alzheimer's disease (AD), while the research progress on DYRK1A inhibitors seemed to be in a bottleneck period. In this work, we identified 32 (ZJCK-6-46) as the most potential DYRK1A inhibitor (IC 50 = 0.68 nM) through rational design, systematic structural optimization, and comprehensive evaluation. Compound 32 exhibited acceptable in vitr… Show more
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