ArticleScientific reports2018
A novel triple combination of pharmacological chaperones improves F508del-CFTR correction.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Disease-causing mutations in the G protein β5 β-propeller disrupt its chaperonin-mediated folding trajectory.bioRxiv : the preprint server for biology · 2025Article
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- ATP-dependent thermoring basis for the heat unfolding of the first nucleotide-binding domain isolated from human CFTR.Research square · 2024Article
- Pulmonary Ionocytes Regulate Airway Surface Liquid pH in Primary Human Bronchial Epithelial Cells.American journal of respiratory and critical care medicine · 2024Article
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- Biomolecular Condensation: A New Phase in Cancer Research.Cancer discovery · 2022Review
- Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR.Nature communications · 2022Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway.Scientific reports · 2022Article
- Article
- NBD2 Is Required for the Rescue of Mutant F508del CFTR by a Thiazole-Based Molecule: A Class II Corrector for the Multi-Drug Therapy of Cystic Fibrosis.Biomolecules · 2021Article
- Nasal Epithelial Cell-Based Models for Individualized Study in Cystic Fibrosis.International journal of molecular sciences · 2021Review
- Combination of Selective PARP3 and PARP16 Inhibitory Analogues of Latonduine A Corrects F508del-CFTR Trafficking.ACS omega · 2020Article
- Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells.Nucleic acids research · 2020Article
- Novel therapeutic approaches for the management of cystic fibrosis.Multidisciplinary respiratory medicine · 2020Article
- Bioactive Thymosin Alpha-1 Does Not Influence F508del-CFTR Maturation and Activity.Scientific reports · 2019Article
- Adapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2019Review
- TMEM16A in Cystic Fibrosis: Activating or Inhibiting?Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacological chaperones (e.g. VX-809, lumacaftor) that bind directly to F508del-CFTR and correct its mislocalization are promising therapeutics for Cystic Fibrosis (CF). However to date, individual correctors provide only ~4% improvement in lung function measured as FEV1, suggesting that multiple drugs will be needed to achieve substantial clinical benefit. Here we examine if multiple sites for pharmacological chaperones exist and can be targeted to enhance the rescue of F508del-CFTR with the premise that additive or synergistic rescue by multiple pharmacological chaperones compared to single correctors indicates that they have different sites of action. First, we found that a combination of the pharmacological chaperones VX-809 and RDR1 provide additive correction of F508del-CFTR. Then using cellular thermal stability assays (CETSA) we demonstrated the possibility of a third pharmacologically important site using the novel pharmacological chaperone tool compound 4-methyl-N-[3-(morpholin-4-yl) quinoxalin-2-yl] benzenesulfonamide (MCG1516A). All three pharmacological chaperones appear to interact with the first nucleotide-binding domain (NBD1). The triple combination of MCG1516A, RDR1, and VX-809 restored CFTR function to >20% that of non-CF cells in well differentiated HBE cells and to much higher levels in other cell types. Thus the results suggest the presence of at least three distinct sites for pharmacological chaperones on F508del-CFTR NBD1, encouraging the development of triple corrector combinations.
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