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  • Title: Affinity-based screening of MDM2/MDMX-p53 interaction inhibitors by chemical array: identification of novel peptidic inhibitors.
    Author: Noguchi T, Oishi S, Honda K, Kondoh Y, Saito T, Kubo T, Kaneda M, Ohno H, Osada H, Fujii N.
    Journal: Bioorg Med Chem Lett; 2013 Jul 01; 23(13):3802-5. PubMed ID: 23726030.
    Abstract:
    MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibitor candidates by affinity-based screening using a chemical array has been established. A number of compounds from an in-house compound library, which were immobilized onto a chemical array, were screened for interaction with fluorescence-labeled MDM2 and MDMX proteins. The subsequent fluorescent polarization assay identified several compounds that inhibited MDM2-p53 and MDMX-p53 interactions.
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