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Updated: Jan 22, 2026
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An Iodide-Yellow Fluorescent Protein-Gap Junction-Intercellular Communication Assay
Published on: February 1, 2019
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High-Content Screening Identifies New Inhibitors of Connexin 43 Gap Junctions.
Christèle Picoli1, Emmanuelle Soleilhac2, Agnès Journet2
11Theranexus, Lyon, France.
Assay and Drug Development Technologies
|July 18, 2019
Summary
Researchers screened FDA-approved drugs to find new inhibitors of connexin 43 (Cx43) gap junctions (GJs). A novel assay identified drugs that block GJ communication, revealing microtubule integrity is crucial for Cx43 GJ function.
Area of Science:
- Cellular Biology
- Pharmacology
- Biochemistry
Background:
- Gap junctions (GJs) are protein channels facilitating intercellular communication.
- Connexin 43 (Cx43) forms the most common GJ channel, crucial in various physiological and pathological conditions.
- Targeting Cx43 GJs offers therapeutic potential for cancer, neurological disorders, and cardiovascular diseases.
Purpose of the Study:
- To develop and validate a high-content screening method for identifying novel Cx43 GJ inhibitors.
- To screen a library of approved drugs for compounds that modulate Cx43 GJ function.
- To investigate the role of cellular structures in Cx43 GJ activity.
Main Methods:
- A high-content screening assay measuring fluorescent dye transfer between adjacent U251 glioblastoma cells expressing Cx43.
- Validation of the assay using known GJ inhibitors like mefloquine.
- Screening of 1,280 FDA- and EMA-approved drugs.
Main Results:
- Identification of known and novel inhibitors of Cx43 GJ channel function from the drug library.
- Confirmation that microtubule integrity is essential for functional Cx43 GJ channels.
- Demonstration of a robust screening platform for GJ modulators.
Conclusions:
- A validated high-content screening method can effectively identify Cx43 GJ inhibitors.
- Approved drugs can serve as a source for novel GJ-targeting therapeutics.
- Microtubule-targeting agents represent a promising class for modulating Cx43 GJ activity.
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