Abstract
Methyl 9-anilinothiazolo[5,4-f]quinazoline-2-carbimidates 1 (EHT 5372) and 2 (EHT 1610) are strong inhibitors of DYRK's family kinases. The crystal structures of the complex revealed a noncanonical binding mode of compounds 1 and 2 in DYRK2, explaining the remarkable selectivity and potency of these inhibitors. The structural data and comparison presented here provide therefore a template for further improvement of this inhibitor class and for the development of novel inhibitors selectively targeting DYRK kinases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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Humans
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Models, Molecular
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Molecular Structure
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Phosphorylation
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / metabolism
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Quinazolines / chemical synthesis
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Quinazolines / chemistry
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Quinazolines / pharmacology*
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Structure-Activity Relationship
Substances
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EHT 1610
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EHT 5372
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Protein Kinase Inhibitors
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Quinazolines
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Protein-Tyrosine Kinases