| Literature DB >> 30095246 |
Anna Czarna1, Jinhua Wang2, Diana Zelencova3, Yao Liu2, Xianming Deng2, Hwan Geun Choi2, Tinghu Zhang2, Wenjun Zhou2, Jae Won Chang2, Hanne Kildalsen1, Ole Morten Seternes1, Nathanael S Gray2, Richard A Engh3, Ulli Rothweiler3.
Abstract
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.Entities:
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Year: 2018 PMID： 30095246 DOI： 10.1021/acs.jmedchem.7b01847
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446