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Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors

Permanent lenke
https://hdl.handle.net/10037/14980
DOI
https://doi.org/10.1021/acs.jmedchem.7b01847
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Åpne
article.pdf (1.699Mb)
Accepted manuscript version (PDF)
Dato
2018-08-10
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Czarna, Anna Lucja; Jinhua, Wang; Zelencova, Diana; Liu, Yao; Deng, Xianming; Choi, Hwan Geun; Zhang, Tinghu; Zhou, Wenjun; Chang, Jae Won; Kildalsen, Hanne; Seternes, Ole Morten; Gray, Nathanael S.; Engh, Richard Alan; Rothweiler, Ulli
Sammendrag
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.
Beskrivelse
Accepted manuscript version. Published version available at https://doi.org/10.1021/acs.jmedchem.7b01847.
Forlag
American Chemical Society
Sitering
Czarna, A.L., Wang, J., Zelencova, D., Liu, Y., Deng, X., Choi, H.G. ... Rothweiler, U. (2018). Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors. Journal of Medicinal Chemistry, 61(17), 7560-7572. https://doi.org/10.1021/acs.jmedchem.7b01847
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