Abstract
A new inhibitor of p53-HDM2 interaction was isolated from a culture of marine-derived fungus, Arthrinium sp. The structure was identified to be (-)-hexylitaconic acid (1) by spectroscopic analysis. The inhibition of p53-HDM2 binding was tested by the ELISA method, and 1 inhibited the binding with an IC(50) value of 50 microg/mL. Although a number of synthetic inhibitors of p53-HDM2 interaction have been reported so far, 1 is the second inhibitor isolated from natural resources.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ascomycota / metabolism*
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Chemistry, Pharmaceutical / methods*
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Design*
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Enzyme Inhibitors / pharmacology*
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Enzyme-Linked Immunosorbent Assay
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Fungal Proteins / chemistry
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Humans
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Inhibitory Concentration 50
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Models, Chemical
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Protein Binding
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Proto-Oncogene Proteins c-mdm2 / metabolism*
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Succinates / chemistry*
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Tumor Suppressor Protein p53 / chemistry*
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Tumor Suppressor Protein p53 / metabolism
Substances
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2-methylene-3-hexylbutanedioic acid
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Enzyme Inhibitors
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Fungal Proteins
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Succinates
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2