Abstract
Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Biological Products / chemistry
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Biological Products / pharmacology*
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Drug Evaluation, Preclinical*
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Hepacivirus / drug effects
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Humans
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Janus Kinase 2 / antagonists & inhibitors*
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Janus Kinase 2 / metabolism
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Kinetics
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
Substances
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Antiviral Agents
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Biological Products
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Protein Kinase Inhibitors
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Small Molecule Libraries
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JAK2 protein, human
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Janus Kinase 2