Abstract
The disruption of the p53-Hdm2 protein-protein interaction induces cell growth arrest and apoptosis. We have identified the 1,4-benzodiazepine-2,5-dione scaffold as a suitable template for inhibiting this interaction by binding to the Hdm2 protein. Several compounds have been made with improved potency, solubility, and cell-based activities.
MeSH terms
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Apoptosis / drug effects
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Benzodiazepines / chemical synthesis
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Benzodiazepines / chemistry
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Benzodiazepines / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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Humans
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Molecular Structure
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Protein Binding / drug effects
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Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
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Proto-Oncogene Proteins c-mdm2 / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / metabolism
Substances
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Tumor Suppressor Protein p53
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Benzodiazepines
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2