Abstract
Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a protein kinase with diverse functions in cell regulation. Abnormal expression and activity of DYRK1A contribute to numerous human malignancies, Down syndrome, and Alzheimer's disease. Notably, DYRK1A has been proposed as a potential therapeutic target for the treatment of diabetes because of its key role in pancreatic β-cell proliferation. Consequently, DYRK1A is an attractive drug target for a variety of diseases. Here, we report the identification of several DYRK1A inhibitors using our in-house topological water network-based approach. All inhibitors were further verified by in vitro assay.
Keywords:
DYRK1A; molecular docking; molecular dynamics simulation; topological water network.
MeSH terms
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Computational Chemistry
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Dyrk Kinases
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 / chemistry*
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Humans
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Ligands
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Molecular Dynamics Simulation*
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / chemistry*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Small Molecule Libraries
Substances
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Ligands
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Protein Kinase Inhibitors
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Small Molecule Libraries
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Glycogen Synthase Kinase 3