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Publication Abstract from PubMed

DYRK1A is one of five members of the dual-specificity tyrosine (Y) phosphorylation-regulated kinase (DYRK) family. The DYRK1A gene is located in the Down syndrome critical region and regulates cellular processes related to proliferation and differentiation of neuronal progenitor cells during early development. This has focused research on its role in neuronal degenerative diseases, including Alzheimer's and Down syndrome. Recent studies have also shown a possible role of DYRK1A in diabetes. Here we report a variety of scaffolds not generally known for DYRK1A inhibition, demonstrating their effects in in vitro assays and also in cell cultures. These inhibitors effectively block the tau phosphorylation that is a hallmark of Alzheimer's disease. The crystal structures of these inhibitors support the design of optimized and novel therapeutics.

Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors.,Czarna A, Wang J, Zelencova D, Liu Y, Deng X, Choi HG, Zhang T, Zhou W, Chang JW, Kildalsen H, Seternes OM, Gray NS, Engh RA, Rothweiler U J Med Chem. 2018 Aug 23. doi: 10.1021/acs.jmedchem.7b01847. PMID:30095246^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.