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

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity Research project
Defending: ,
Publication language English (en)
Title in original language Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors
Field of research 3. Medical and Health sciences
Sub-field of research 3.1 Basic medicine including pharmacy
Authors Anna Czarna
Jinhua Wang
Diāna Zeļencova
Yao Liu
Xianming Deng
Hwan Geun Choi
Tinghu Zhang
Wenjun Zhou
Jae Won Chang
Hanne Kildalsen
Ole Morten Seternes
Nathanael S. Gray
Rhichard A. Engh
Ulli Rothweiler
Keywords
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.
DOI: 10.1021/acs.jmedchem.7b01847
Hyperlink: https://pubs.acs.org/doi/10.1021/acs.jmedchem.7b01847 
Reference Czarna, A., Wang, J., Zeļencova, D., Liu, Y., Deng, X., Choi, H., Zhang, T., Zhou, W., Chang, J., Kildalsen, H., Seternes, O., Gray, N., Engh, R., Rothweiler, U. Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors. Journal of Medicinal Chemistry, 2018, Vol.61, Iss.17, pp.7560-7572. ISSN 0022-2623. e-ISSN 1520-4804. Available from: doi:10.1021/acs.jmedchem.7b01847
Additional information Citation count:
ID 27831