Affinity-based screening of MDM2/MDMX–p53 interaction inhibitors by chemical array: Identification of novel peptidic inhibitors
Open accessAbstract
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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- Authors
- Noguchi, T., Oishi, S., Honda, K., Kondoh, Y., Saito, T., Kubo, T., Kaneda, M., Ohno, H., Osada, H., & Fujii, N.
- Affiliations
- Kyoto University (JP)
- RIKEN Advanced Science Institute (JP)
- Corresponding author
- Oishi, Shinya
- Fujii, Nobutaka
- Venue
- Bioorganic & Medicinal Chemistry Letters
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 23
- Issue
- 13
- Pages
- 3802-3805
- ISSN
- 0960-894X (ISSN-L)
- OpenAlex
- W2060280797
- Cited by
- 24
- References
- 29
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 2
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bioorganic & Medicinal Chemistry Letters (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (24659046, 23510287)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- MDM2, MDMX, p53, protein-protein interaction inhibitors, peptide inhibitors, anticancer agents, tumor suppressor regulation
- MeSH terms
- Dose-Response Relationship, Drug, Humans, Models, Molecular, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Structure-Activity Relationship, Molecular Structure, Tumor Suppressor Protein p53, Cell Cycle Proteins, Proto-Oncogene Proteins c-mdm2, High-Throughput Screening Assays
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