Kappel, Sven; Melek, Korollus; Ross-Kaschitza, Daniela; Hauert, Barbara; Gerber, Christian E.; Lochner, Martin; Peinelt, Christine (2024). CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells. Frontiers in Pharmacology, 15 Frontiers 10.3389/fphar.2024.1369513
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Introduction: Upon activation at low pH, TMEM206 conducts Cl− ions across plasma and vesicular membranes. In a (patho)physiological context, TMEM206 was reported to contribute to acid-induced cell death in neurons, kidney and cervical epithelial cells. We investigated the role of TMEM206 in acidinduced cell death in colorectal cancer cells. In addition, we studied CBA as a new small molecule inhibitor for TMEM206.
Methods: The role of TMEM206 in acid-induced cell death was studied with CRISPR/Cas9-mediated knockout and FACS analysis. The pharmacology of TMEM206 was determined with the patch clamp technique.
Results: In colorectal cancer cells, TMEM206 is not a critical mediator of acidinduced cell death. CBA is a small molecule inhibitor of TMEM206 (IC50 = 9.55 μM) at low pH, at pH 6.0 inhibition is limited.
Conclusion: CBA demonstrates effective and specific inhibition of TMEM206; however, its inhibitory efficacy is limited at pH 6.0. Despite this limitation, CBA is a potent inhibitor for functional studies at pH 4.5 and may be a promising scaffold for the development of future TMEM206 inhibitors.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Kappel, Sven, Melek, Korollus, Ross, Daniela, Hauert, Barbara, Gerber, Christian Elias, Lochner, Martin, Peinelt, Christine |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health 500 Science > 540 Chemistry |
ISSN: |
1663-9812 |
Publisher: |
Frontiers |
Language: |
English |
Submitter: |
Martin Lochner |
Date Deposited: |
15 Mar 2024 13:02 |
Last Modified: |
15 Mar 2024 13:02 |
Publisher DOI: |
10.3389/fphar.2024.1369513 |
BORIS DOI: |
10.48350/194042 |
URI: |
https://boris.unibe.ch/id/eprint/194042 |
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