ArticleScience advances2024
A uniquely efficacious type of CFTR corrector with complementary mode of action.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.Pharmaceutics · 2026Review
- A novel drug series optimized to address cystic fibrosis and other CFTR deficiency diseases of human airways.npj drug discovery · 2025Article
- Genetically engineered approaches to the treatment of cystic fibrosis.Biophysical reviews · 2025Review
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- 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
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Article
- Cystic fibrosis: new challenges and perspectives beyond elexacaftor/tezacaftor/ivacaftor.Therapeutic advances in respiratory diseaseReview
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Three distinct pharmacological corrector types (I, II, III) with different binding sites and additive behavior only partially rescue the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) folding and trafficking defect observed in cystic fibrosis. We describe uniquely effective, macrocyclic CFTR correctors that were additive to the known corrector types, exerting a complementary "type IV" corrector mechanism. Macrocycles achieved wild-type-like folding efficiency of F508del-CFTR at the endoplasmic reticulum and normalized CFTR currents in reconstituted patient-derived bronchial epithelium. Using photo-activatable macrocycles, docking studies and site-directed mutagenesis a highly probable binding site and pose for type IV correctors was identified in a cavity between lasso helix-1 (Lh1) and transmembrane helix-1 of membrane spanning domain (MSD)-1, distinct from the known corrector binding sites. Since only F508del-CFTR fragments spanning from Lh1 until MSD2 responded to type IV correctors, these likely promote cotranslational assembly of Lh1, MSD1, and MSD2. Previously corrector-resistant CFTR folding mutants were also robustly rescued, suggesting substantial therapeutic potential for type IV correctors.
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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.