ArticleThe Journal of membrane biology2003
Inhibition of the endogenous volume-regulated anion channel (VRAC) in HEK293 cells by acidic di-aryl-ureas.
Article in The Journal of membrane biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
- Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO-101 in adult male and female volunteers.Basic & clinical pharmacology & toxicology · 2020Trial
- Binding to Albumin and Off-Target Toxicity Confound the Use of LRRC8/VRAC Channel Blockers in Cell Physiology Assays.bioRxiv : the preprint server for biology · 2026Article
- LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism.The Journal of physiology · 2026Article
- LRRC8A: A multifaceted regulator in cancer, neurological disorders, metabolic diseases and immune modulation.Genes & diseases · 2026Review
- Mechanism of action of two potent LRRC8/VRAC channel inhibitors.Research square · 2026Article
- NitrOFF: An Engineered Fluorescent Biosensor to Illuminate Nitrate Transport in Living Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Inhibition of ABCG2 by SCO-101 Enhances Chemotherapy Efficacy in Cancer.International journal of molecular sciences · 2025Article
- NitrOFF: An engineered fluorescent biosensor to illuminate nitrate transport in living cells.bioRxiv : the preprint server for biology · 2025Article
- A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC).Channels (Austin, Tex.) · 2022Review
- Caveolin-3 prevents swelling-induced membrane damage via regulation of IBiophysical journal · 2022Article
- LRRC8A is essential for volume-regulated anion channel in smooth muscle cells contributing to cerebrovascular remodeling during hypertension.Cell proliferation · 2021Article
- Electrophysiological study of Arabidopsis ABCB4 and PIN2 auxin transporters: Evidence of auxin activation and interaction enhancing auxin selectivity.Plant direct · 2021Article
- LRRC8A is essential for hypotonicity-, but not for DAMP-induced NLRP3 inflammasome activation.eLife · 2020Article
- LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CaFrontiers in cell and developmental biology · 2020Article
- Natural and synthetic flavonoids, novel blockers of the volume-regulated anion channels, inhibit endothelial cell proliferation.Pflugers Archiv : European journal of physiology · 2018Article
- Molecular Biology and Physiology of Volume-Regulated Anion Channel (VRAC).Current topics in membranes · 2018Review
- Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects.British journal of pharmacology · 2017Article
- Relationship between TMEM16A/anoctamin 1 and LRRC8A.Pflugers Archiv : European journal of physiology · 2016Article
- Biophysics and Physiology of the Volume-Regulated Anion Channel (VRAC)/Volume-Sensitive Outwardly Rectifying Anion Channel (VSOR).Pflugers Archiv : European journal of physiology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endogenous volume-regulated anion channel (VRAC) from HEK293 cells was pharmacologically characterized using the whole-cell patch-clamp technique. Under isotonic conditions a small (1.3 nS), Ca(2+)-independent Cl conductance was measured. However, swelling at 75% tonicity activated a VRAC identified as an outward-rectifying anion current ( P(l) > P(Cl) > P(gluconate)), which was ATP-dependent and showed inactivation at positive potentials. Activation of this current followed a sigmoid time course, reaching a plateau conductance of 42.6 nS after 12-15 min ( t(1/2) = 7 min). The pharmacology of this VRAC was investigated using standard Cl(-)-channel blockers (NPPB, DIDS, and tamoxifen) as well as a new group (acidic di-aryl ureas) of Cl(-)-channel blockers (NS1652, NS3623, NS3749, and NS3728). The acidic di-aryl ureas were originally synthezised for inhibition of the human erythrocyte Cl(-) conductance in vivo. NS3728 was the most potent VRAC blocker in this series ( IC(50) = 0.40 micro M) and even more potent than tamoxifen (2.2 micro M). NS3728 accelerated channel inactivation at positive potentials. These results show that acidic di-aryl ureas constitute a promising starting point for the synthesis of potent inhibitors of VRAC.
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