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Updated: Jun 9, 2025
Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions
Published on: January 7, 2019
Development of a high-throughput screening system targeting the protein-protein interactions between PRL and CNNM
Yosuke Funato1, Mai Mimura2, Kazuto Nunomura3
1Laboratory of Biorecognition Chemistry, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan. funato.yosuke.3i@kyoto-u.ac.jp.
Researchers developed a novel screening system to identify compounds that inhibit the oncogenic Phosphatase of regenerating liver (PRL) protein from interacting with cyclin M (CNNM) proteins, aiding in new anti-cancer drug development.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Phosphatase of regenerating liver (PRL) is an oncogenic protein.
- PRL promotes tumor progression by inhibiting cyclin M (CNNM) Mg2+ efflux activity.
- Targeting the PRL-CNNM interaction is a potential anti-cancer strategy.
Purpose of the Study:
- To develop a high-throughput screening system to detect PRL-CNNM interactions.
- To identify novel inhibitors of the PRL-CNNM interaction.
- To characterize potential anti-cancer drug candidates.
Main Methods:
- Homogenous time-resolved fluorescence resonance energy transfer (HTRF) assay.
- Optimization of recombinant CNNM4 CBS domains and PRL3 protein constructs.
- High-throughput screening of compound libraries.
Main Results:
- A robust HTRF assay for detecting PRL-CNNM interaction was established.
- Several compounds inhibiting the PRL-CNNM interaction were identified.
- A promising candidate compound showed stability, cellular activity, and favorable drug-like properties.
Conclusions:
- The developed screening system is effective for identifying PRL-CNNM interaction inhibitors.
- The identified compounds, particularly the candidate, show potential for anti-cancer drug development.
- This work contributes to developing novel therapeutic strategies targeting PRL-driven cancers.
