Abstract
Mental retardation is the most common and debilitating condition for individuals with Down syndrome (DS). The hyper-activation of DYRK1A by overexpression causes significant learning and memory deficits in DS-model mice. Thus far, no mechanism-based drug has been developed to address this. After a combination of in silico and in vitro screenings, two DYRK1A inhibitors were isolated that are active in a cell-based assay. Further optimization could lead to a novel drug discovery that could address DS learning and memory deficits.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids / chemistry
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Animals
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Binding Sites
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Disease Models, Animal
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Down Syndrome / drug therapy*
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Down Syndrome / physiopathology
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Dyrk Kinases
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydrogen Bonding
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Learning Disabilities / drug therapy
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Learning Disabilities / physiopathology
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Memory Disorders / drug therapy
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Memory Disorders / physiopathology
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Mice
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Molecular Structure
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
Substances
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Amino Acids
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Enzyme Inhibitors
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases