ArticleCell death & disease2019
Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Lysosome-Targeted Squaramide Anion Transporters.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant "autophagy checkpoint".Aging cell · 2023Review
- Light-Driven Photoconversion of Squaramides with Implications in Anion Transport.Organic letters · 2023Article
- Article
- Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry.Biomedicines · 2022Review
- Photomodulation of Transmembrane Transport and Potential by Stiff-Stilbene Based Bis(thio)ureas.Journal of the American Chemical Society · 2022Article
- Self-assembly of an anion receptor with metal-dependent kinase inhibition and potent in vitro anti-cancer properties.Nature communications · 2021Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 6 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis is a disease caused by defective function of a chloride channel coupled to a blockade of autophagic flux. It has been proposed to use synthetic chloride transporters as pharmacological agents to compensate insufficient chloride fluxes. Here, we report that such chloride anionophores block autophagic flux in spite of the fact that they activate the pro-autophagic transcription factor EB (TFEB) coupled to the inhibition of the autophagy-suppressive mTORC1 kinase activity. Two synthetic chloride transporters (SQ1 and SQ2) caused a partially TFEB-dependent relocation of the autophagic marker LC3 to the Golgi apparatus. Inhibition of TFEB activation using a calcium chelator or calcineurin inhibitors reduced the formation of LC3 puncta in cells, yet did not affect the cytotoxic action of SQ1 and SQ2 that could be observed after prolonged incubation. In conclusion, the squaramide-based synthetic chloride transporters studied in this work (which can also dissipate pH gradients) are probably not appropriate for the treatment of cystic fibrosis yet might be used for other indications such as cancer.
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Registered trials
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