title: Affinity-based screening of MDM2/MDMX-p53 interaction inhibitors by chemical array: identification of novel peptidic inhibitors.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Noguchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Kaori
authors.initials: K
authors.lastname: Honda
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Kondoh
authors.forename: Tamio
authors.initials: T
authors.lastname: Saito
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kubo
authors.forename: Masato
authors.initials: M
authors.lastname: Kaneda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D018797:Cell Cycle Proteins; D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2