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Updated: Apr 17, 2026
Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
Published on: June 30, 2023
Use of cell-based screening to identify small-molecule compounds that modulate claudin-4 expression
Akihiro Watari1, Maki Hashegawa, Thanchanok Muangman
1Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan, akihiro@phs.osaka-u.ac.jp.
Abstract:
Claudins constitute a family of at least 27 proteins with four transmembrane domains, and play a pivotal role in maintaining tight-junctions seals in diverse epithelial tissues. The expression of claudin-4 often changes in intestinal tissues of inflammatory bowel disease and various human cancers. Therefore, claudin-4 is a promising target for treatment of these diseases. In our previous study, we established a reporter cell line to monitor claudin-4 expression on the basis of a functional claudin-4 promoter. Using this cell line, we have performed a cell-based screen of a library containing 2642 biologically active small-molecule compounds to identify modulators of claudin-4 expression. The screen identified 24 potential modulators of the claudin-4 promoter activity. Fourteen of these compounds (12 of them novel) induced endogenous claudin-4 expression. The identified compounds might serve as lead compounds targeting aberrant gene expression in inflammatory bowel disease.
Insights
Researchers screened small molecules to find compounds that modulate claudin-4 expression, a protein implicated in inflammatory bowel disease and cancer. Fourteen compounds successfully induced claudin-4 expression, offering potential therapeutic leads.
Area of Science:
- Molecular Biology
- Cell Biology
- Pharmacology
Background:
- Claudins are integral membrane proteins crucial for tight junction integrity in epithelial tissues.
- Claudin-4 expression is dysregulated in inflammatory bowel disease (IBD) and human cancers, making it a potential therapeutic target.
- Previous work established a reporter cell line to track claudin-4 promoter activity.
Purpose of the Study:
- To identify small-molecule compounds that modulate claudin-4 expression.
- To discover potential therapeutic agents for diseases associated with aberrant claudin-4 levels, such as IBD.
Main Methods:
- A cell-based screen of 2642 biologically active small-molecule compounds was conducted.
- A reporter cell line, based on a functional claudin-4 promoter, was utilized to monitor gene expression.
- Compounds were assessed for their ability to modulate claudin-4 promoter activity.
Main Results:
- The screen identified 24 potential modulators of claudin-4 promoter activity.
- Fourteen of these compounds, including 12 novel ones, successfully induced endogenous claudin-4 expression.
- These compounds demonstrated efficacy in modulating the target gene's expression.
Conclusions:
- The identified small molecules represent promising lead compounds for targeting claudin-4.
- These compounds may offer a novel therapeutic strategy for inflammatory bowel disease and other conditions linked to claudin-4 dysregulation.
- Further investigation into these modulators could lead to new treatments.
