Cited by 1,088Cystic Fibrosis Research AdvancesIon Transport and Channel RegulationInhalation and Respiratory Drug Delivery

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809

Open access

Van Goor, Fredrick, Hadida, Sabine, Grootenhuis, Peter D. J., Burton, Bill, Stack, Jeffrey H., Straley, Kimberly S., Decker, Caroline J., Miller, Mark, McCartney, Jason, Olson, Eric R., Wine, Jeffrey J., Frizzell, Ray A., Ashlock, Melissa, Negulescu, Paul A.·2011·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1105787108PMC PMC3219147

Open this paper in CoChat — free account

Abstract

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC 50 , 81 ± 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR.

Integrity signals

Registry

Crossref · 10.1073/pnas.1105787108

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA
Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., et al. (1989) · Science · doi:10.1126/science.2475911 · Cited by 7,418
Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis
Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O’Riordan, C. R., & Smith, A. E. (1990) · Cell · doi:10.1016/0092-8674(90)90148-8 · Cited by 1,792
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive
Denning, G. M., Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E., & Welsh, M. J. (1992) · Nature · doi:10.1038/358761a0 · Cited by 1,236
Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770
Goor, F. V., Hadidaꝉ, S., Grootenhuis, P. D. J., Burton, B., Cao, D., Neuberger, T., Turnbull, A., Singh, A. K., Joubran, J., Hazlewood, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904709106 · Cited by 1,225
Self-citation
Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report
Farrell, P. M., Rosenstein, B. J., White, T. B., Accurso, F. J., Castellani, C., Cutting, G. R., Durie, P. R., LeGrys, V. A., Massie, J., Parad, R. B., et al. (2008) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2008.05.005 · Cited by 1,093
Cystic fibrosis: A worldwide analysis ofCFTR mutations?correlation with incidence data and application to screening
Bobadilla, J. L., Macek, M., Fine, J. P., & Farrell, P. M. (2002) · Human Mutation · doi:10.1002/humu.10041 · Cited by 1,032
Effect of VX-770 in Persons with Cystic Fibrosis and the G551D- CFTR Mutation
Accurso, F. J., Rowe, S. M., Clancy, J. P., Boyle, M., Dunitz, J., Durie, P. R., Sagel, S. D., Hornick, D. B., Konstan, M. W., Donaldson, S. H., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909825 · Cited by 803
Self-citation
Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation
Dalemans, W., Barbry, P., Champigny, G., Jallat, S., Jallat, S., Dott, K., Dreyer, D., Crystal, R. G., Pavirani, A., Lecocq, J.-P., et al. (1991) · Nature · doi:10.1038/354526a0 · Cited by 707
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice
Castellani, C., Cuppens, H., Maçek, M., Cassiman, J. J., Kerem, E., Durie, P. R., Tullis, E. D., Assael, B. M., Bombieri, C., Brown, A., et al. (2008) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2008.03.009 · Cited by 624
Small-molecule correctors of defective F508-CFTR cellular processing identified by high-throughput screening
Pedemonte, N. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24898 · Cited by 551

Show all 44 references

Research works printed but not linked: 1

; Cystic Fibrosis Foundation US Cystic Fibrosis Patient Registry (Cystic Fibrosis Foundation, Bethesda, 2002).

Sorted by citations

Items 301–400 of 1,000

Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
Vu, C. B., Bridges, R. J., Peña‐Rasgado, C., Lacerda, A. E., Bordwell, C., Sewell, A. L., Nichols, A. J., Chandran, S., Lonkar, P., Picarella, D., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01539 · Cited by 43
Effects of Pseudomonas aeruginosa on CFTR chloride secretion and the host immune response
Stanton, B. A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00373.2016 · Cited by 45
High-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorder
Schmunk, G., Nguyen, R. L., Ferguson, D. L., Kumar, K., Parker, I., & Gargus, J. J. (2017) · Scientific Reports · doi:10.1038/srep40740 · Cited by 44
High-Throughput Screening for Readthrough Modulators of CFTR PTC Mutations
Liang, F., Shang, H., Jordan, N. J., Wong, E., Mercadante, D. L., Saltz, J., Mahiou, J., Bihler, H. J., & Mense, M. (2017) · SLAS TECHNOLOGY · doi:10.1177/2472630317692561 · Cited by 42
Mutation-specific downregulation of CFTR2 variants by gating potentiators
Avramescu, R. G., Kai, Y., Xu, H., Bidaud-Meynard, A., Schnúr, A., Frenkiel, S., Matouk, E., Veit, G., & Lukacs, G. L. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx367 · Cited by 43
Cisvariants identified in F508del complex alleles modulate CFTR channel rescue by small molecules
Baatallah, N., Bitam, S., Martin, N., Servel, N., Costes, B., Mekki, C., Chevalier, B., Pranke, I. M., Simonin, J., Girodon, E., et al. (2017) · Human Mutation · doi:10.1002/humu.23389 · Cited by 47
Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells
Awatade, N. T., Wong, S. L., Capraro, A., Pandžić, E., Šlapetová, I., Zhong, L., Turgutoğlu, N., Fawcett, L. K., Whan, R. M., Jaffé, A., et al. (2021) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2020.12.019 · Cited by 39
Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis
Pinto, M. C., Silva, I. A. L., Figueira, M. F., Amaral, M. D., & Lopes‐Pacheco, M. (2021) · Journal of Experimental Pharmacology · doi:10.2147/jep.s255377 · Cited by 44
Small-molecule drugs for cystic fibrosis: Where are we now?
Laselva, O., Guerra, L., Castellani, S., Favia, M., Gioia, S. D., & Conese, M. (2021) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2021.102098 · Cited by 43
CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine
McDonald, E. F., Meiler, J., & Plate, L. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.3c00310 · Cited by 44
Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer
Zhou, X., Wang, G., Tian, C., Du, L., Prochownik, E. V., & Li, Y. (2024) · Nature Communications · doi:10.1038/s41467-024-50138-x · Cited by 47
Increased efficacy of VX ‐809 in different cellular systems results from an early stabilization effect of F508del‐ CFTR
Farinha, C. M., Sousa, M., Canato, S., Schmidt, A., Uliyakina, I., & Amaral, M. D. (2015) · Pharmacology Research & Perspectives · doi:10.1002/prp2.152 · Cited by 43
Managing the Underlying Cause of Cystic Fibrosis: A Future Role for Potentiators and Correctors
Galietta, L. J. V. (2013) · Pediatric Drugs · doi:10.1007/s40272-013-0035-3 · Cited by 43
Cystic Fibrosis Transmembrane Conductance Regulator–Modifying Medications: The Future of Cystic Fibrosis Treatment
Pettit, R. S. (2012) · Annals of Pharmacotherapy · doi:10.1345/aph.1r076 · Cited by 43
Lipophilicity of the Cystic Fibrosis Drug, Ivacaftor (VX-770), and Its Destabilizing Effect on the Major CF-causing Mutation: F508del
Chin, S., Hung, M., Won, A. M., Wu, Y.-S., Ahmadi, S., Yang, D., Elmallah, S., Toutah, K., Hamilton, C. M., Young, R. N., et al. (2018) · Molecular Pharmacology · doi:10.1124/mol.118.112177 · Cited by 43
Tezacaftor for the treatment of cystic fibrosis
Sala, M. A., & Jain, M. (2018) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2018.1507741 · Cited by 47
A posttranslational modification code for CFTR maturation is altered in cystic fibrosis
Pankow, S., Bamberger, C., & Yates, J. R. (2019) · Science Signaling · doi:10.1126/scisignal.aan7984 · Cited by 42
Theranostics by testing CFTR modulators in patient-derived materials: The current status and a proposal for subjects with rare CFTR mutations
Amaral, M. D., Boeck, K. D., Amaral, M. D., Davies, J. C., Boeck, K. D., Dřevı́nek, P., Elborn, J. S., Kerem, E., & Lee, T. (2019) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2019.06.010 · Cited by 43
Long QT Syndrome Type 2: Emerging Strategies for Correcting Class 2 KCNH2 (hERG) Mutations and Identifying New Patients
Ono, M., Burgess, D. E., Schroder, E. A., Elayi, C. S., Anderson, C. L., January, C. T., Sun, B., Immadisetty, K., Kekenes-Huskey, P. M., & Delisle, B. P. (2020) · Biomolecules · doi:10.3390/biom10081144 · Cited by 43
Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer’s disease
Liu, H., Luo, K., & Luo, D. (2018) · Scientific Reports · doi:10.1038/s41598-018-21256-6 · Cited by 42
Cystic Fibrosis – a Multiorgan Protein Misfolding Disease
Fraser-Pitt, D. J., & O′Neil, D. A. (2015) · Future Science OA · doi:10.4155/fso.15.57 · Cited by 42
Genetics of Cystic Fibrosis
Egan, M. E. (2015) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2015.11.002 · Cited by 49
Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis
Lopes‐Pacheco, M., Boinot, C., Sabirzhanova, I. B., Rapino, D., & Cebotaru, L. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000475578 · Cited by 42
Clinically approved CFTR modulators rescue Nrf2 dysfunction in cystic fibrosis airway epithelia
Borcherding, D. C., Siefert, M. E., Lin, S., Brewington, J. J., Sadek, H. A., Clancy, J. P., Plafker, S. M., & Ziady, A. G. (2019) · Journal of Clinical Investigation · doi:10.1172/jci96273 · Cited by 42
Recent Advances And New Perspectives In Targeting CFTR For Therapy Of Cystic Fibrosis And Enterotoxin-Induced Secretory Diarrheas
Zhang, W., Fujii, N., & Naren, A. P. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.1 · Cited by 41
Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum
Poothong, J., Jang, I., & Kaufman, R. J. (2021) · Progress in molecular and subcellular biology · doi:10.1007/978-3-030-67696-4_6 · Cited by 41
Fixing cystic fibrosis by correcting CFTR domain assembly
Okiyoneda, T., & Lukács, G. L. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201208083 · Cited by 43
Generation and functional characterization of epithelial cells with stable expression of SLC26A9 Cl− channels
Salomon, J. J., Spahn, S., Wang, X., Füllekrug, J., Bertrand, C. A., & Mall, M. A. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00321.2015 · Cited by 42
Molecular modelling and molecular dynamics of CFTR
Callebaut, I., Hoffmann, B., Lehn, P., & Mornon, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2385-9 · Cited by 44
Endoplasmic reticulum–associated degradation of the renal potassium channel, ROMK, leads to type II Bartter syndrome
O'Donnell, B. M., Mackie, T. D., Subramanya, A. R., & Brodsky, J. L. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.786376 · Cited by 41
Peripheral Protein Quality Control as a Novel Drug Target for CFTR Stabilizer
Fukuda, R., & Okiyoneda, T. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01100 · Cited by 41
Two CFTR mutations within codon 970 differently impact on the chloride channel functionality
Amato, F., Scudieri, P., Musante, I., Tomati, V., Caci, E., Comegna, M., Maietta, S., Manzoni, F. M. P., Lullo, A. M. D., Wachter, E. D., et al. (2019) · Human Mutation · doi:10.1002/humu.23741 · Cited by 41
Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators
Estabrooks, S. K., & Brodsky, J. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020452 · Cited by 44
The bidirectional relationship between CFTR and lipids
Cottrill, K. A., Farinha, C. M., & McCarty, N. A. (2020) · Communications Biology · doi:10.1038/s42003-020-0909-1 · Cited by 41
Long-term safety and efficacy of lumacaftor–ivacaftor therapy in children aged 6–11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study
Chilvers, M. A., Davies, J. C., Milla, C. E., Tian, S., Han, Z., Cornell, A. G., Owen, C. A., & Ratjen, F. A. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30517-8 · Cited by 41
Long-term safety of lumacaftor–ivacaftor in children aged 2–5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study
Hoppe, J. E., Chilvers, M. A., Ratjen, F. A., McNamara, J., Owen, C. A., Tian, S., Zahigian, R., Cornell, A. G., & McColley, S. A. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(21)00069-2 · Cited by 41
Correctors of mutant CFTR enhance subcortical cAMP–PKA signaling through modulating ezrin phosphorylation and cytoskeleton organization
Abbattiscianni, A. C., Favia, M., Mancini, M. T., Cardone, R. A., Guerra, L., Monterisi, S., Castellani, S., Laselva, O., Sole, F. D., Conese, M., et al. (2016) · Journal of Cell Science · doi:10.1242/jcs.177907 · Cited by 43
Creation and characterization of an airway epithelial cell line for stable expression of CFTR variants
Gottschalk, L., Vecchio-Pagán, B., Sharma, N., Han, S. T., Franca, A., Wohler, E., Batista, D., Goff, L. A., & Cutting, G. R. (2015) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2015.11.010 · Cited by 40
Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity
Farinha, C. M., Swiatecka‐Urban, A., Brautigan, D. L., & Jordan, P. (2016) · Frontiers in Chemistry · doi:10.3389/fchem.2016.00001 · Cited by 40
Promise and Potential Peril With Lumacaftor for the Trafficking Defective Type 2 Long-QT Syndrome-Causative Variants, p.G604S, p.N633S, and p.R685P, Using Patient-Specific Re-Engineered Cardiomyocytes
O’Hare, B. J., Kim, C. S. J., Hamrick, S. K., Ye, D., Tester, D. J., & Ackerman, M. J. (2020) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.120.002950 · Cited by 41
Airway Epithelial Inflammation In Vitro Augments the Rescue of Mutant CFTR by Current CFTR Modulator Therapies
Gentzsch, M., Cholon, D. M., Quinney, N. L., Martino, M. E. B., Minges, J. T., Boyles, S. E., Lee, T. N. G., Esther, C. R., & Ribeiro, C. M. P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.628722 · Cited by 40
Pharmacological chaperone approaches for rescuing GPCR mutants: Current state, challenges, and screening strategies
Beerepoot, P., Nazari, R., & Salahpour, A. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.12.036 · Cited by 39
Emerging preclinical modulators developed for F508del-CFTR have the potential to be effective for ORKAMBI resistant processing mutants
Laselva, O., Bartlett, C., Popa, A., Ouyang, H., Gunawardena, T. N. A., Gonska, T. Y., Moraes, T. J., & Bear, C. E. (2020) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2020.07.015 · Cited by 39
Personalized medicine for cystic fibrosis: Establishing human model systems
Mou, H., Brazauskas, K., & Rajagopal, J. (2015) · Pediatric Pulmonology · doi:10.1002/ppul.23233 · Cited by 40
Gene therapy in cystic fibrosis
Prickett, M. H., & Jain, M. (2012) · Translational research · doi:10.1016/j.trsl.2012.12.001 · Cited by 41
On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator
Yu, Y., Sohma, Y., & Hwang, T. (2016) · The Journal of Physiology · doi:10.1113/jp271723 · Cited by 40
A Split-Luciferase-Based Trimer Formation Assay as a High-throughput Screening Platform for Therapeutics in Alport Syndrome
Omachi, K., Kamura, M., Teramoto, K., Kojima, H., Yokota, T., Kaseda, S., Kuwazuru, J., Fukuda, R., Koyama, K., Matsuyama, S., et al. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.02.003 · Cited by 39
Discovery of ABBV/GLPG-3221, a Potent Corrector of CFTR for the Treatment of Cystic Fibrosis
Scanio, M. J. C., Searle, X. B., Liu, B., Koenig, J. R., Altenbach, R. J., Gfesser, G. A., Bogdan, A. R., Greszler, S. N., Zhao, G., Singh, A. K., et al. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00377 · Cited by 39
Cystic fibrosis gene mutations: evaluation and assessment of disease severity
Elborn, J. S., & Vallières, É. (2014) · Advances in Genomics and Genetics · doi:10.2147/agg.s53768 · Cited by 43
The investigational Cystic Fibrosis drug Trimethylangelicin directly modulates CFTR by stabilizing the first membrane-spanning domain
Laselva, O., Molinski, S. V., Casavola, V., & Bear, C. E. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.09.005 · Cited by 38
In vitro Methods for the Development and Analysis of Human Primary Airway Epithelia
Gianotti, A., Delpiano, L., & Caci, E. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01176 · Cited by 38
Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutants
van Willigen, M., Vonk, A. M., Yeoh, H. Y., Kruisselbrink, E., Kleizen, B., van der Ent, C. K., Egmond, M. R., de Jonge, H. R., Braakman, I., Beekman, J. M., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201800172 · Cited by 38
Biochemistry of very-long-chain and long-chain ceramides in cystic fibrosis and other diseases: The importance of side chain
Garić, D., Sanctis, J. B. D., Shah, J., Dumut, D. C., & Radzioch, D. (2019) · Progress in Lipid Research · doi:10.1016/j.plipres.2019.03.001 · Cited by 39
The influence of CFTR complex alleles on precision therapy of cystic fibrosis
Chevalier, B., & Hinzpeter, A. (2019) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2019.12.008 · Cited by 41
Physiologically Based Pharmacokinetic Modeling of CFTR Modulation in People with Cystic Fibrosis Transitioning from Mono or Dual Regimens to Triple-Combination Elexacaftor/Tezacaftor/Ivacaftor
Tsai, A., Wu, S.-P., Haseltine, E. L., Kumar, S., Moskowitz, S. M., Panorchan, P., & Shah, K. (2020) · Pulmonary Therapy · doi:10.1007/s41030-020-00124-7 · Cited by 41
A Precision Medicine Approach to Optimize Modulator Therapy for Rare CFTR Folding Mutants
Veit, G., Velkov, T., Xu, H., Vadeboncoeur, N., Bilodeau, L., Matouk, E., & Lukács, G. L. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11070643 · Cited by 37
A new platform for high-throughput therapy testing on iPSC-derived lung progenitor cells from cystic fibrosis patients
Jiang, J. X., Wellhauser, L., Laselva, O., Utkina, I., Bozóky, Z., Gunawardena, T. N. A., Ngan, Z., Xia, S., Paola, M. D., Eckford, P. D. W., et al. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.09.020 · Cited by 37
Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough
Lee, R. E., Lewis, C. A., He, L., Bulik‐Sullivan, E. C., Gallant, S. C., Mascenik, T., Dang, H., Cholon, D. M., Gentzsch, M., Morton, L. C., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154571 · Cited by 38
New Therapeutic Approaches to Modulate and Correct Cystic Fibrosis Transmembrane Conductance Regulator
Ong, T., & Ramsey, B. W. (2016) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2016.04.006 · Cited by 39
CFTR potentiators: from bench to bedside
Jih, K., Lin, W., Sohma, Y., & Hwang, T. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.09.015 · Cited by 39
Inhibition of histone-deacetylase activity rescues inflammatory cystic fibrosis lung disease by modulating innate and adaptive immune responses
Bodas, M., Mazur, S., Min, T., & Vij, N. (2018) · Respiratory Research · doi:10.1186/s12931-017-0705-8 · Cited by 37
Pharmacoperone drugs: targeting misfolded proteins causing lysosomal storage-, ion channels-, and G protein-coupled receptors-associated conformational disorders
Hou, Z.-S., Ulloa‐Aguirre, A., & Tao, Y. (2018) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2018.1480367 · Cited by 38
Molecular Mechanism of Action of Trimethylangelicin Derivatives as CFTR Modulators
Laselva, O., Marzaro, G., Vaccarin, C., Lampronti, I., Tamanini, A., Lippi, G., Gambari, R., Cabrini, G., Bear, C. E., Chilin, A., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00719 · Cited by 37
Targeted Activation of Cystic Fibrosis Transmembrane Conductance Regulator
Villamizar, O., Waters, S. A., Scott, T. A., Saayman, S. M., Grepo, N., Urak, R. Z., Davis, A. M., Jaffé, A., & Morris, K. V. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.07.002 · Cited by 39
Genetic, cell biological, and clinical interrogation of theCFTR mutation c.3700 A>G (p.Ile1234Val) informs strategies for future medical intervention
Molinski, S. V., Gonska, T. Y., Huan, L., Baskin, B., Janahi, I. A., Ray, P. N., & Bear, C. E. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.4 · Cited by 37
β 2 -Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis
Vijftigschild, L. A. W., Berkers, G., Dekkers, J. F., Ommen, D. D. Z.-V., Matthes, E., Kruisselbrink, E., Vonk, A. M., Hensen, C. E., Heida-Michel, S., Geerdink, M., et al. (2016) · European Respiratory Journal · doi:10.1183/13993003.01661-2015 · Cited by 38
Update in Cystic Fibrosis 2014
Ong, T., & Ramsey, B. W. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201504-0656up · Cited by 36
Anchored PDE4 regulates chloride conductance in wild‐type and ΔF508‐CFTR human airway epithelia
Blanchard, E., Zlock, L. T., Lao, A., Mika, D., Namkung, W., Xie, M., Scheitrum, C., Gruenert, D. C., Verkman, A. S., Finkbeiner, W. E., et al. (2013) · The FASEB Journal · doi:10.1096/fj.13-240861 · Cited by 36
Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis
Esposito, S., Tosco, A., Villella, V. R., Raia, V., Kroemer, G., & Maiuri, L. (2016) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-016-0040-z · Cited by 39
Entry to Chiral 1,1,2,3-Tetrasubstituted Arylcyclopropanes by Pd(II)-Catalyzed Arylation via Directing Group-Mediated C(sp3)-H Activation
Hoshiya, N., Kondo, M., Fukuda, H., Arisawa, M., Uenishi, J., & Shuto, S. (2017) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.6b02935 · Cited by 36
A Proteomic Variant Approach (ProVarA) for Personalized Medicine of Inherited and Somatic Disease
Hutt, D. M., Loguercio, S., Campos, A. R., & Balch, W. E. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.06.017 · Cited by 35
R560S: A class II CFTR mutation that is not rescued by current modulators
Awatade, N. T., Ramalho, S. S., Silva, I. A. L., Felício, V., Botelho, H. M., de Poel, E., Vonk, A. M., Beekman, J. M., Farinha, C. M., & Amaral, M. D. (2018) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2018.07.001 · Cited by 36
A novel triple combination of pharmacological chaperones improves F508del-CFTR correction
Carlile, G. W., Yang, Q., Matthes, E., Liao, J., Radinovic, S., Miyamoto, C. M., Robert, R., Hanrahan, J. W., & Thomas, D. Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-29276-y · Cited by 36
Small molecule‐facilitated anion transporters in cells for a novel therapeutic approach to cystic fibrosis
Fiore, M., Cossu, C., Capurro, V., Picco, C., Ludovico, A., Mielczarek, M., Carreira‐Barral, I., Caci, E., Baroni, D., Quesada, R., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14649 · Cited by 39
Anti-Infectives Restore ORKAMBI® Rescue of F508del-CFTR Function in Human Bronchial Epithelial Cells Infected with Clinical Strains of P. aeruginosa
Laselva, O., Stone, T. A., Bear, C. E., & Deber, C. M. (2020) · Biomolecules · doi:10.3390/biom10020334 · Cited by 36
The preclinical discovery and development of the combination of ivacaftor + tezacaftor used to treat cystic fibrosis
Guerra, L., Favia, M., Gioia, S. D., Laselva, O., Bisogno, A., Casavola, V., Colombo, C., & Conese, M. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1750592 · Cited by 36
Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
Silva, I. A. L., Laselva, O., & Lopes‐Pacheco, M. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12081321 · Cited by 36
Correctors Rescue CFTR Mutations in Nucleotide‐Binding Domain 1 (NBD1) by Modulating Proteostasis
Lopes‐Pacheco, M., Sabirzhanova, I. B., Rapino, D., Morales, M. M., Guggino, W. B., & Cebotaru, L. (2016) · ChemBioChem · doi:10.1002/cbic.201500620 · Cited by 36
Individualized medicine using intestinal responses to CFTR potentiators and correctors
Beekman, J. M. (2016) · Pediatric Pulmonology · doi:10.1002/ppul.23553 · Cited by 36
Patient-derived cell models for personalized medicine approaches in cystic fibrosis
Ramalho, A. S., Amato, F., & Gentzsch, M. (2022) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2022.11.007 · Cited by 37
Combinatorial prediction of therapeutic perturbations using causally inspired neural networks
Gonzalez, G., Lin, X., Herath, I. S., Veselkov, K., Bronstein, M. M., & Žitnik, M. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01481-x · Cited by 45
Roscovitine is a proteostasis regulator that corrects the trafficking defect of F 508del‐ CFTR by a CDK ‐independent mechanism
Norez, C., Vandebrouck, C., Bertrand, J., Noël, S., Durieu, É., Oumata, N., Galons, H., Antigny, F., Chatelier, A., Bois, P., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12859 · Cited by 35
Repairing the basic defect in cystic fibrosis – one approach is not enough
Farinha, C. M., & Matos, P. (2015) · FEBS Journal · doi:10.1111/febs.13531 · Cited by 35
Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770
Gentzsch, M., Ren, H. Y., Houck, S. A., Quinney, N. L., Cholon, D. M., Sopha, P., Chaudhry, I. G., Das, J., Dokholyan, N. V., Randell, S. H., et al. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00186.2016 · Cited by 35
CFTR rescue with VX-809 and VX-770 favors the repair of primary airway epithelial cell cultures from patients with class II mutations in the presence of Pseudomonas aeruginosa exoproducts
Adam, D., Bilodeau, C., Sognigbé, L., Maillé, É., Ruffin, M., & Brochiero, E. (2018) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2018.03.010 · Cited by 35
A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector
Yanda, M. K., Liu, Q., & Cebotaru, L. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001846 · Cited by 35
Lumacaftor/ Ivacaftor improves exercise tolerance in patients with Cystic Fibrosis and severe airflow obstruction
Wark, P. A. B., Cookson, K., Thiruchelvam, T., Brannan, J. D., & Dorahy, D. J. (2019) · BMC Pulmonary Medicine · doi:10.1186/s12890-019-0866-y · Cited by 37
Phenotyping of Rare CFTR Mutations Reveals Distinct Trafficking and Functional Defects
Ensinck, M. M., Keersmaecker, L. D., Heylen, L., Ramalho, A. S., Gijsbers, R., Farré, R., Boeck, K. D., Christ, F., Debyser, Z., & Carlon, M. S. (2020) · Cells · doi:10.3390/cells9030754 · Cited by 34
Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis
Baker, E. H., Harris, W. T., Rowe, S. M., Rutland, S. B., & Oates, G. R. (2020) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2020.09.011 · Cited by 35
Distinct proteostasis states drive pharmacologic chaperone susceptibility for cystic fibrosis transmembrane conductance regulator misfolding mutants
McDonald, E. F., Sabusap, C. M. P., Kim, M., & Plate, L. (2022) · Molecular Biology of the Cell · doi:10.1091/mbc.e21-11-0578 · Cited by 34
Allosteric Coupling between the Intracellular Coupling Helix 4 and Regulatory Sites of the First Nucleotide-binding Domain of CFTR
Dawson, J. E., Farber, P. J., & Forman-Kay, J. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074347 · Cited by 34
Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2-(3-Phenylpropylamino) Benzoate
Lin, W., Sohma, Y., & Hwang, T. (2016) · Molecular Pharmacology · doi:10.1124/mol.116.104570 · Cited by 34
Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools
Liessi, N., Cichero, E., Pesce, E., Arkel, M., Salis, A., Tomati, V., Paccagnella, M., Damonte, G., Tasso, B., Galietta, L. J. V., et al. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.12.030 · Cited by 34
Physiological and pharmacological characterization of the N1303K mutant CFTR
DeStefano, S., Gees, M., & Hwang, T. (2018) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2018.05.011 · Cited by 34
Adapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease
Bodas, M., & Vij, N. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00020 · Cited by 34
Palladium-catalyzed α-arylation for the addition of small rings to aromatic compounds
He, Z., & Hartwig, J. F. (2019) · Nature Communications · doi:10.1038/s41467-019-12090-z · Cited by 34
Medically Important Alterations in Transport Function and Trafficking of ABCG2
Homolya, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062786 · Cited by 35
Impact of the cystic fibrosis mutation F508del-CFTR on renal cyst formation and growth
Li, H., Yang, W., Mendes, F., Amaral, M. D., & Sheppard, D. N. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00130.2012 · Cited by 34
Stabilizing Rescued Surface-Localized ΔF508 CFTR by Potentiation of Its Interaction with Na+/H+ Exchanger Regulatory Factor 1
Arora, K., Moon, C., Zhang, W., Yarlagadda, S., Penmatsa, H., Ren, A., Sinha, C., & Naren, A. P. (2014) · Biochemistry · doi:10.1021/bi401263h · Cited by 34
Investigating Internalization and Intracellular Trafficking of GPCRs: New Techniques and Real-Time Experimental Approaches
Foster, S. R., & Bräuner‐Osborne, H. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_57 · Cited by 37

Authors: Van Goor, F., Hadida, S., Grootenhuis, P. D. J., Burton, B., Stack, J. H., Straley, K. S., Decker, C. J., Miller, M., McCartney, J., Olson, E. R., Wine, J. J., Frizzell, R. A., Ashlock, M., & Negulescu, P. A.
Affiliations: Vertex Pharmaceuticals, San Diego, CA 92121;
Vertex Pharmaceuticals (United States) (US)
Stanford University (US)
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; and
Cystic Fibrosis Foundation (US)
Corresponding author: Negulescu, Paul A.
ORCID: Miller, Mark
Olson, Eric R.
Wine, Jeffrey J.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2011-10-05
Volume: 108
Issue: 46
Pages: 18843-18848
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1105787108
PMC: PMC3219147
OpenAlex: W2071407356
Cited by: 1,088
References: 44
Citations by year: 2026: 24 · 2025: 48 · 2024: 48 · 2023: 57 · 2022: 64 · 2021: 83 · 2020: 98 · 2019: 95 · 2018: 101 · 2017: 103 · 2016: 77 · 2015: 85 · 2014: 84 · 2013: 61 · 2012: 58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Cystic Fibrosis Foundation Therapeutics
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Keywords: cystic fibrosis, F508del-CFTR, CFTR correctors, lumacaftor, endoplasmic reticulum retention, chloride secretion, bronchial epithelial cells, CFTR mutations
MeSH terms: Aminopyridines, Bronchi, Cell Line, Cells, Cultured, Chemistry, Pharmaceutical, Chlorides, Cystic Fibrosis, Drug Evaluation, Preclinical, Epithelial Cells, Homozygote, Humans, Lung, Models, Genetic, Mutation, Drug Design, Cystic Fibrosis Transmembrane Conductance Regulator, Benzodioxoles, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks