ArticleEMBO molecular medicine2013
Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 80 citations in OpenAlex.
- Mechanistic Insights into CFTR Potentiation by the Antimicrobial Peptide Esc(1-21): Direct Interaction with the NBD1-NBD2 Interface.ACS omega · 2026Article
- Esc peptides and derivatives potentiate the activity of CFTR with gating defects and display antipseudomonal activity in cystic fibrosis-like lung disease.Cellular and molecular life sciences : CMLS · 2025Article
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- Ligand-based virtual-screening identified a novel CFTR ligand which improves the defective cell surface expression of misfolded ABC transporters.Frontiers in pharmacology · 2024Article
- In Silico and In Vitro Evaluation of the Mechanism of Action of Three VX809-Based Hybrid Derivatives as Correctors of the F508del CFTR Protein.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Elexacaftor Mediates the Rescue of F508del CFTR Functional Expression Interacting with MSD2.International journal of molecular sciences · 2023Article
- Keratin 8 is a scaffolding and regulatory protein of ERAD complexes.Cellular and molecular life sciences : CMLS · 2022Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice.Scientific reports · 2022Article
- Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides.Cellular and molecular life sciences : CMLS · 2021Article
- GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening.Communications biology · 2021Article
- Pharmacological chaperones improve intra-domain stability and inter-domain assembly via distinct binding sites to rescue misfolded CFTR.Cellular and molecular life sciences : CMLS · 2021Article
- New insights into structure and function of bis-phosphinic acid derivatives and implications for CFTR modulation.Scientific reports · 2021Article
- Comprehensive Analysis of Chemical Structures That Have Been Tested as CFTR Activating Substances in a Publicly Available Database CandActCFTR.Frontiers in pharmacology · 2021Article
- Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors.International journal of molecular sciences · 2020Article
- Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure.Molecular diagnosis & therapy · 2019Review
- Article
- Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine.Frontiers in pharmacology · 2019Review
- Molecular basis of cystic fibrosis: from bench to bedside.Annals of translational medicine · 2018Review
- ΔF508-CFTR Modulator Screen Based on Cell Surface Targeting of a Chimeric Nucleotide Binding Domain 1 Reporter.SLAS discovery : advancing life sciences R & D · 2018Article
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Authors and funding
23 authors at 9 institutions in 5 countries.
Funding
Abstract
The deletion of Phe508 (ΔF508) in the first nucleotide binding domain (NBD1) of CFTR is the most common mutation associated with cystic fibrosis. The ΔF508-CFTR mutant is recognized as improperly folded and targeted for proteasomal degradation. Based on molecular dynamics simulation results, we hypothesized that interaction between ΔF508-NBD1 and housekeeping proteins prevents ΔF508-CFTR delivery to the plasma membrane. Based on this assumption we applied structure-based virtual screening to identify new low-molecular-weight compounds that should bind to ΔF508-NBD1 and act as protein-protein interaction inhibitors. Using different functional assays for CFTR activity, we demonstrated that in silico-selected compounds induced functional expression of ΔF508-CFTR in transfected HeLa cells, human bronchial CF cells in primary culture, and in the nasal epithelium of homozygous ΔF508-CFTR mice. The proposed compounds disrupt keratin8-ΔF508-CFTR interaction in ΔF508-CFTR HeLa cells. Structural analysis of ΔF508-NBD1 in the presence of these compounds suggests their binding to NBD1. We conclude that our strategy leads to the discovery of new compounds that are among the most potent correctors of ΔF508-CFTR trafficking defect known to date.
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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.