Abstract
Computer aided modeling guided the design of a series of diarylimidazole compounds (11-22) intended to interact with both the ATP and adjacent allosteric binding domains of B-RAF kinase. Their ability to inhibit the function of B-RAF kinase and intracellular ERK1/2 phosphorylation were evaluated.
MeSH terms
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Adenosine Triphosphate / metabolism
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Allosteric Site
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Computer-Aided Design*
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Crystallography, X-Ray
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Hydrocarbons, Aromatic / chemical synthesis
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Hydrocarbons, Aromatic / pharmacology*
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Imidazoles / chemical synthesis
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Imidazoles / pharmacology*
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Inhibitory Concentration 50
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Hydrocarbons, Aromatic
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Imidazoles
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Protein Kinase Inhibitors
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Adenosine Triphosphate
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Proto-Oncogene Proteins B-raf
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Extracellular Signal-Regulated MAP Kinases