ArticleAmerican journal of respiratory and critical care medicine2016
Discovery of Clinically Approved Agents That Promote Suppression of Cystic Fibrosis Transmembrane Conductance Regulator Nonsense Mutations.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 84 citations in OpenAlex.
- Identification of small molecules that enhance aminoglycoside-mediated suppression ofMolecular therapy. Oncology · 2026Article
- Comparative evaluation of TRIDs : a strategy to improve treatments.Journal of translational medicine · 2026Article
- Barriers to the Pharmacologic Rescue of W1282X CFTR.Biochemistry · 2026Article
- Article
- Ophthalmologic Manifestations in Bardet-Biedl Syndrome: Emerging Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025Article
- Beyond the 10%: Unraveling the genetic diversity in Turkish cystic fibrosis patients not eligible for CFTR modulators.Pediatric pulmonology · 2024Article
- Identification of novel small molecule-based strategies of COL7A1 upregulation and readthrough activity for the treatment of recessive dystrophic epidermolysis bullosa.Scientific reports · 2024Article
- Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process.PLoS biology · 2023Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- The synthetic aminoglycoside ELX-02 induces readthrough of G550X-CFTR producing superfunctional protein that can be further enhanced by CFTR modulators.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- 2-Guanidino-quinazoline promotes the readthrough of nonsense mutations underlying human genetic diseases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Gene-specific nonsense-mediated mRNA decay targeting for cystic fibrosis therapy.Nature communications · 2022Article
- Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Comprehensive Analysis of Combinatorial Pharmacological Treatments to Correct Nonsense Mutations in the CFTR Gene.International journal of molecular sciences · 2021Article
- Functional correction of CFTR mutations in human airway epithelial cells using adenine base editors.Nucleic acids research · 2021Article
- A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion.Nature communications · 2021Article
- Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia.International journal of molecular sciences · 2021Article
- Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021Review
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
rationalePremature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Several agents are known to suppress PTCs but are poorly efficacious or toxic.
objectivesTo determine whether there are clinically available agents that elicit translational readthrough and improve CFTR function sufficient to confer therapeutic benefit to patients with CF with PTCs.
methodsTwo independent screens, firefly luciferase and CFTR-mediated transepithelial chloride conductance assay, were performed on a library of 1,600 clinically approved compounds using fisher rat thyroid cells stably transfected with stop codons. Select agents were further evaluated using secondary screening assays including short circuit current analysis on primary cells from patients with CF. In addition, the effect of CFTR modulators (ivacaftor) was tested in combination with the most efficacious agents. MEASUREMENTS AND MAIN
resultsFrom the primary screen, 48 agents were selected as potentially active. Following confirmatory tests in the transepithelial chloride conductance assay and prioritizing agents based on favorable pharmacologic properties, eight agents were advanced for secondary screening. Ivacaftor significantly increased short circuit current following forskolin stimulation in cells treated with pyranoradine tetraphosphate, potassium p-aminobenzoate, and escin as compared with vehicle control. Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR expression and function in vitro.
conclusionsClinically approved drugs identified as potential readthrough agents, in combination with ivacaftor, may induce nonsense suppression to restore therapeutic levels of CFTR function. One or more agents may be suitable to advance to human testing.
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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.