Abstract
By using a phage display derived peptide as an initial template, compounds have been developed that are highly specific against Mdm2/Mdm4. These compounds exhibit greater potency in p53 activation and protein-protein interaction assays than a compound derived from the p53 wild-type sequence. Unlike Nutlin, a small molecule inhibitor of Mdm2/Mdm4, the phage derived compounds can arrest cells resistant to p53 induced apoptosis over a wide concentration range without cellular toxicity, suggesting they are highly suitable for cyclotherapy.
MeSH terms
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Cell Cycle Proteins
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Humans
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Models, Molecular
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism
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Peptides / chemistry
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Peptides / pharmacology*
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / metabolism
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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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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Cell Cycle Proteins
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MDM4 protein, human
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Nuclear Proteins
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Peptides
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2