ArticleNature chemical biology2013
Mechanism-based corrector combination restores ΔF508-CFTR folding and function.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
237 citing papers in PubMed, 2 syntheses or guidelines pooled it, 386 citations in OpenAlex.
- Ivacaftor-tezacaftor-elexacaftor, tezacaftor-ivacaftor and lumacaftor-ivacaftor for treating cystic fibrosis: a systematic review and economic evaluation.Health technology assessment (Winchester, England) · 2025Pooled it
- Integrative genomic meta-analysis reveals novel molecular insights into cystic fibrosis and ΔF508-CFTR rescue.Scientific reports · 2020Pooled it
- Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.Pharmaceutics · 2026Review
- A cell-permeable nanobody to restore F508del cystic fibrosis transmembrane conductance regulator activity.Nature chemical biology · 2026Article
- Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65.JACS Au · 2026Article
- Cigarette Smoke Induces Canonical Stress Granule Formation in Human Bronchial Epithelial Cells in Reactive Oxygen Species- and PERK-Dependent Manners.Biomolecules · 2026Article
- Single-molecule dissection of CFTR folding defects and pharmacological rescue.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations.Cellular and molecular life sciences : CMLS · 2026Article
- In vivo conformational space and defects of misfolded CFTR variants by covalent protein painting.Nature communications · 2025Article
- Bioinformatics identification of key genes correlating NOD1 and Endoplasmic Reticulum stress in Hepatitis B virus-induced acute liver failure.Scientific reports · 2025Article
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators.iScience · 2025Article
- Functional rescue of F508del-CFTR through revertant mutations introduced by CRISPR base editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Target Identification with Live-Cell Photoaffinity Labeling and Mechanism of Action Elucidation of ARN23765, a Highly Potent CFTR Corrector.Journal of medicinal chemistry · 2025Article
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- Inflammatory response in CF airway epithelial cells: a comparative study of modulators and wild-type CFTR rescue.Frontiers in pharmacology · 2025Article
- The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent CaRespiratory research · 2024Article
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Molecular Phenotypes Segregate Missense Mutations in SLC13A5 Epilepsy.Journal of molecular biology · 2024Article
- Effect of CFTR Modulators on Oxidative Stress and Autophagy in Non-CFTR-Expressing Cells.International journal of molecular sciences · 2024Article
177 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
The most common cystic fibrosis mutation, ΔF508 in nucleotide binding domain 1 (NBD1), impairs cystic fibrosis transmembrane conductance regulator (CFTR)-coupled domain folding, plasma membrane expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and an incompletely understood mechanism, hampering drug development. Given the effect of second-site suppressor mutations, robust ΔF508-CFTR correction most likely requires stabilization of NBD1 energetics and the interface between membrane-spanning domains (MSDs) and NBD1, which are both established primary conformational defects. Here we elucidate the molecular targets of available correctors: class I stabilizes the NBD1-MSD1 and NBD1-MSD2 interfaces, and class II targets NBD2. Only chemical chaperones, surrogates of class III correctors, stabilize human ΔF508-NBD1. Although VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional plasma membrane expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in cystic fibrosis bronchial epithelial cells and intestinal organoids. Thus, the combination of structure-guided correctors represents an effective approach for cystic fibrosis therapy.
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Registered trials
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.