Abstract
The evaluation of a sulfonamide inhibitor of the p53-mdm2 interaction is presented. The compound was identified using 3D database searching techniques based on a computationally derived pharmacophore model of mdm2 binding. It inhibits the physical interaction of recombinant p53 and mdm2 in vitro and increases p53-dependent transcription in an mdm2-overexpressing cell line.
Copyright 2004 American Chemical Society
MeSH terms
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Cell Line, Tumor
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Databases, Factual
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Genes, Reporter
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Humans
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Luciferases / biosynthesis
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Luciferases / genetics
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / metabolism*
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Protein Binding / drug effects
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-mdm2
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Quantitative Structure-Activity Relationship
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
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Transcriptional Activation
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Nuclear Proteins
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Proto-Oncogene Proteins
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Sulfonamides
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Tumor Suppressor Protein p53
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Luciferases
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2