Abstract
Extracellular signal-regulated kinase 2 (ERK2) has become an attractive target for the development of therapeutics for the treatment of cancer. We have been able to identify eight new inhibitors of ERK2 by means of a drug design protocol involving the virtual screening with docking simulations and in vitro enzyme assay. The newly discovered inhibitors can be categorized into three structural classes and reveal a significant potency with IC(50) values ranging from 1 to 30 microM. Therefore, all of the three inhibitor scaffolds deserve further development by structure-activity relationship or de novo design methods. Structural features relevant to the stabilizations of the newly identified inhibitors in the ATP-binding site of ERK2 are discussed in detail.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / chemistry
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Binding Sites
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 1 / chemistry
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Models, Chemical
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Models, Molecular
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Models, Statistical
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Molecular Conformation
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Neoplasms / drug therapy*
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Adenosine Triphosphate
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Mitogen-Activated Protein Kinase 1
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p38 Mitogen-Activated Protein Kinases