ArticleeLife2019
Cystic fibrosis drug ivacaftor stimulates CFTR channels at picomolar concentrations.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- Triple potentiator combinations increase the functional correction of several CFTR gating mutants.npj drug discovery · 2026Article
- Altered functional interactions between CFTR disease mutants ΔF508 and G551D and the protein kinase A catalytic subunit.The Journal of physiology · 2026Article
- Chronic and acute modulator treatment restore wild-type-like activity and stability to the primary cystic fibrosis-causingProceedings of the National Academy of Sciences of the United States of America · 2026Article
- In vivo conformational space and defects of misfolded CFTR variants by covalent protein painting.Nature communications · 2025Article
- Molecular and pharmacological evaluation of rare, cystic fibrosis-causing missense mutations of the CFTR channel.The Journal of physiology · 2025Article
- The potentiator ivacaftor is essential for pharmacological restoration of F508del-CFTR function and mucociliary clearance in cystic fibrosis.JCI insight · 2025Article
- CFTR negatively reprograms Th2 cell responses, and CFTR potentiation restrains allergic airway inflammation.JCI insight · 2025Article
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- CFTR as a therapeutic target for severe lung infection.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Structural determinants of protein kinase A essential for CFTR channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Structure-based discovery of CFTR potentiators and inhibitors.bioRxiv : the preprint server for biology · 2024Article
- Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor.Molecules (Basel, Switzerland) · 2024Review
- Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.The Journal of physiology · 2024Article
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
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- Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor-Ivacaftor.Frontiers in pharmacology · 2023Review
- In Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The devastating inherited disease cystic fibrosis (CF) is caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channel. The recent approval of the CFTR potentiator drug ivacaftor (Vx-770) for the treatment of CF patients has marked the advent of causative CF therapy. Currently, thousands of patients are being treated with the drug, and its molecular mechanism of action is under intensive investigation. Here we determine the solubility profile and true stimulatory potency of Vx-770 towards wild-type (WT) and mutant human CFTR channels in cell-free patches of membrane. We find that its aqueous solubility is ~200 fold lower (~60 nanomolar), whereas the potency of its stimulatory effect is >100 fold higher, than reported, and is unexpectedly fully reversible. Strong, but greatly delayed, channel activation by picomolar Vx-770 identifies multiple sequential slow steps in the activation pathway. These findings provide solid guidelines for the design of
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.