Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors
Journal of Medicinal Chemistry 2018
Anna Czarna, Jinhua Wang, Diāna Zeļencova-Gopejenko, 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

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

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

Publication language
English (en)
The Scientific Library of the Riga Technical University.
E-mail: uzzinas@rtu.lv; Phone: +371 28399196