lumacaftor (VX-809) / Vertex 
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 9 Diseases   1 Trial   1 Trial   672 News 


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  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  E-pharmacophore based virtual screening of potent lead molecules against Cystic Fibrosis: An in silico study. (Pubmed Central) -  Dec 13, 2024   
    The compound Anguibactin (NPC41982) has been identified as a top lead that exhibits higher binding affinity and stability than the reference compound Lumacaftor, suggesting their potential to bind to the active site of the CFTR protein. These compounds could serve as starting points for the development of drug-like molecules for treating cystic fibrosis.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  The ER Stress Induced in Human Neuroblastoma Cells Can Be Reverted by Lumacaftor, a CFTR Corrector. (Pubmed Central) -  Sep 27, 2024   
    Here, we evaluated the activity of Vx-809 (Lumacaftor), a drug used in cystic fibrosis, in SH-SY5Y neuronal cells, in which an ER stress condition was induced by Thapsigargin, to verify whether the drug could improve protein folding, suggesting its possible therapeutic use in proteinopathies, such as neurodegenerative diseases (NDs). Our data show that Vx-809 is involved in the significant reduction in protein produced under ER stress, particularly in the levels of Bip, ATF4, and ATF6 by Western blotting analysis, the reduction in ROS in the cytosol and mitochondria, and the reduction in the activation of the apoptotic pathway, measured by flow cytofluorimetry analysis and in restoring calcium homeostasis.
  • ||||||||||  Development of a drug testing platform for CFTR premature termination codon variants based on rectal organoids () -  Sep 4, 2024 - Abstract #NACFC2024NACFC_1011;    
    Incubation with the aminoglycoside G418, as expected from the literature, caused a significantly greater in FIS rate than control (vehicle) and ELX-02 or PTC124, with further improvement in combination with CFTR modulators (elexacaftor/tezacaftor/ivacaftor [ETI]). Our preliminary data indicate that the levels of swelling induced by G418+ETI reached reference AUC values of F508del/F508del organoids treated with VX809/ VX770 (mean 2,487.9
  • ||||||||||  elexacaftor (VX-445) / Vertex, lumacaftor (VX-809) / Vertex
    Off-target identification of cystic fibrosis pharmacological correctors using functionalized photocrosslinker analogs () -  Sep 4, 2024 - Abstract #NACFC2024NACFC_991;    
    Background: Cystic fibrosis (CF) pharmacological correctors such as VX-809 and VX-445 are used widely in combinations as highly effective modulator therapy (HEMT) at CF clinics because of their efficacy in improving CFTR protein trafficking and function, yet several side-effects from these correctors and adverse drug interactions have been reported, emphasizing the need to understand the etiology of side-effects that may arise from off-target use. The off targets identified may provide insights into indirect correction mechanisms and provide explanations for the side-effects observed in patients at the cellular level, allowing further optimization of corrector combinations to enhance efficacy and decrease adverse effects.
  • ||||||||||  Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex, tezacaftor (VX-661) / Vertex
    Journal:  Identification of 6,9-dihydro-5H-pyrrolo[3,2-h]quinazolines as a new class of F508del-CFTR correctors for the treatment of cystic fibrosis. (Pubmed Central) -  Aug 10, 2024   
    Synergy was also observed with corr-4a (class 2 corrector) but not with VX-445 and PP028 (class 3 correctors) indicating that the new compounds behave as class 3 correctors. These results suggest that tricyclic pyrrolo-quinazolines interact with CFTR at a site different from that of VX-809 and represent a novel class of CFTR correctors suitable for combinatorial pharmacological treatments for the basic defect in CF.
  • ||||||||||  lumacaftor (VX-809) / Vertex, exaluren (ELX-02) / Eloxx Pharma, eragidomide (CC-90009) / BMS
    Rescue of CFTR nonsense mutations is enhanced under inflammatory stimuli (157 A-C) -  Jul 4, 2024 - Abstract #NACFC2024NACFC_549;    
    These results suggest that tricyclic pyrrolo-quinazolines interact with CFTR at a site different from that of VX-809 and represent a novel class of CFTR correctors suitable for combinatorial pharmacological treatments for the basic defect in CF. Cells were also treated in the last 24 hours with ELX-02 (200
  • ||||||||||  Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex
    Review, Journal:  Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor. (Pubmed Central) -  Feb 28, 2024   
    In this review, we exploit the organic synthesis of ivacaftor, tezacaftor, and elexacaftor by providing a retrosynthetic drug analysis for these CFTR modulators. Furthermore, we describe the current understanding of the mechanisms of action (MoA's) of these compounds by discussing several studies that report the key findings on the molecular mechanisms underlying their action on the CFTR protein.
  • ||||||||||  elexacaftor (VX-445) / Vertex, posenacaftor (PTI-801) / Kineta
    Journal:  PTI-801 (posenacaftor) shares a common mechanism with VX-445 (elexacaftor) to rescue p.Phe508del-CFTR. (Pubmed Central) -  Feb 26, 2024   
    Despite the high efficacy of PTI-801 in combination with ABBV-2222, FDL-169, VX-661, or VX-809, these dual corrector combinations only partially restored p.Phe508del-CFTR conformational stability, as shown by the lower half-life of the mutant protein compared to that of WT-CFTR. In summary, PTI-801 likely shares a common MoA with VX-445 in rescuing p.Phe508del-CFTR, thus being a feasible alternative for the development of novel corrector combinations with greater capacity to rescue mutant CFTR folding and stability.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  Cyclic diacyl thioureas enhance activity of corrector Lumacaftor on F508del-CFTR. (Pubmed Central) -  Feb 19, 2024   
    All compounds proved to be non-cytotoxic against different cancer cell lines. Good pharmacokinetic properties were predicted for derivatives 5 and 6, thus supporting the value of these compounds for the development of novel modulators potentially useful for cystic fibrosis.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Trial completion, Trial completion date, Trial primary completion date:  Bioequivalence and Food Effect Bioavailability Study of Lumacaftor Film-Coated Tablets (clinicaltrials.gov) -  Dec 25, 2023   
    P1,  N=39, Completed, 
    Good pharmacokinetic properties were predicted for derivatives 5 and 6, thus supporting the value of these compounds for the development of novel modulators potentially useful for cystic fibrosis. Recruiting --> Completed
  • ||||||||||  Kalydeco (ivacaftor) / Vertex
    Journal:  Synthesis and Evaluation of Ivacaftor Derivatives with Reduced Lipophilicity. (Pubmed Central) -  Dec 11, 2023   
    Molecular modeling predicts that the increased polarity of compound 3 allows engagement with polar amino acids present in the binding pocket with hydrogen bonding and ionic interactions, which are collectively higher in strength as compared to hydrophobic interactions that stabilize ivacaftor. Overall, the data suggests that reduced lipophilicity may improve the efficacy of this class of CFTR potentiators when used for folding-rescued ?F508-CFTR.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study. (Pubmed Central) -  Oct 9, 2023   
    The virtual screening with 165 different ion channel inhibitors from the ion channel library shows monovalent ion channel blockers, namely lumacaftor, glipizide, gliquidone, glisoxepide, and azelnidipine to be the inhibitors with high docking scores. Understanding the three-dimensional structure of M protein will help design therapeutics and vaccines for Dengue infection.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  CFTR and PC2, partners in the primary cilia in ADPKD. (Pubmed Central) -  Jul 31, 2023   
    Our data suggest that CFTR is present in the cilia and plays a role there, perhaps through its conductance of Cl. We also postulate that septin 2 is important for localizing CFTR to the apical membrane in cystic epithelia.
  • ||||||||||  lumacaftor (VX-809) / Vertex, tezacaftor (VX-661) / Vertex, galicaftor (GLPG2222) / AbbVie
    Journal:  Computational Exploration of Potential CFTR Binding Sites for Type I Corrector Drugs. (Pubmed Central) -  Jul 12, 2023   
    This data may serve to better understand the structural changes induced by mutation of CFTR and how correctors bind to the protein. Additionally, it may aid in the design of new, more effective CFTR corrector drugs.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Tasigna (nilotinib) / Novartis, Inhibikase
    A NOVEL PROGNOSTIC MODEL OF DLBCL PATIENTS BASED ON CUPROPTOSIS RELATED GENES (Poster area) -  May 12, 2023 - Abstract #EHA2023EHA_1388;    
    The outcome of this study may establish a solid foundation to screen repurposed and natural compounds as potential antiviral therapeutics against different highly pathogenic viruses. A prognostic model based on 5 cuproptosis-related genes was constructed, and 3 potential targeted inhibitors of CDKN2A were screened out by molecular docking.
  • ||||||||||  elexacaftor (VX-445) / Vertex, lumacaftor (VX-809) / Vertex
    A Drug Screening System for Cystic Fibrosis Utilizing Stem-cell and Functional Imaging Technologies (Walter E. Washington Convention Center, Area D, Hall C (Lower Level)) -  Mar 25, 2023 - Abstract #ATS2023ATS_8477;    
    Next, we performed phenotypic screening using both MQAE and label-free FIS assay on drug repositioning library, resulting in identification of candidate compounds. CONCLUSION We established a novel phenotypic screening system by combination of iPSC-based disease models and fluorescent/label-free imaging assays, which will be promising for efficient identification of drug candidates for CF.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Impact of cholesterol on the functioning of CFTR modulators (Hall G1) -  Feb 27, 2023 - Abstract #ECFS2023ECFS_215;    
    Our experiments reveal that cholesterol plays an important role in the functioning of Orkambi and in the interaction of this drug with the membrane. These findings help to better understand the role of cholesterol in CFTR-modulator interactions, further bridging the gap in knowledge relating to existing CF drugs and paving the way for the design of more effective CF treatments.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Review, Journal:  The impact of N-nitrosamine impurities on clinical drug development. (Pubmed Central) -  Jan 29, 2023   
    Consequent interruption or discontinuation of the manufacturing and distribution of several marketed drugs has culminated into shortages of marketed drugs, including the antidiabetic drug metformin and the potentially life-saving drug rifampin for the treatment of tuberculosis...In particular, rifampin is a key clinical index drug employed in drug-drug interaction (DDI) studies, and as a result of nitrosamine impurities regulatory bodies no longer accept the administration of rifampin in DDI studies involving healthy subjects. Drug developers are now forced to look at alternative approaches for commonly employed perpetrators, which will be discussed in this review.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  Impact of cholesterol and Lumacaftor on the folding of CFTR helical hairpins. (Pubmed Central) -  Nov 19, 2022   
    We propose a model whereby VX-809 shields the protein from the lipid environment in a mutant-independent manner such that the WT scaffold prevails. Such 'normalization' to WT conformation is consistent with the action of VX-809 as a protein-folding chaperone.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    FDA event, Journal:  Deep-learning based repurposing of FDA-approved drugs against Candida albicans dihydrofolate reductase and molecular dynamics study. (Pubmed Central) -  Oct 19, 2022   
    Furthermore, analysis of binding free energy corroborated the stability of interactions as they had binding energy of -114.91 kJ mol, -79.22 kJ mol and -78.52 kJ mol for Paritaprevir, Lumacaftor and Rifampin respectively as compared to the reference (-63.10 kJ mol). From the results, we conclude that these drugs have great potential to inhibit CaDHFR and would add to the drug discovery against candidiasis, and hence these drugs for repurposing should be explored further.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Symproic (naldemedine) / Shionogi, Collegium Pharma
    Journal:  Targeting human thymidylate synthase: Ensemble-based virtual screening for drug repositioning and the role of water. (Pubmed Central) -  Oct 19, 2022   
    Further binding free energy calculations based on the Molecular Mechanics Poisson-Boltzmann Surface Area method revealed that Imatinib, Lumacaftor and Naldemedine scored -130.7 ± 28.1, -210.6 ± 29.9 and -238.0 ± 25.4 kJ/mol, respectively, showing good binding affinity for the candidates considered. Overall, the analysis of the molecular dynamics trajectory of the receptor-drug complexes revealed stable structures for Imatinib, Lumacaftor and Naldemedine, for the entire simulation time.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Treatment of Autosomal Recessive Polycystic Kidney Disease With CFTR Modulators (Exhibit Hall, Orange County Convention Center, West Building) -  Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_3808;    
    These data suggest that in the absence of FPC, CFTR is degraded and mislocalized. Demonstration of liver cyst reduction increases the therapeutic potential of VX-809 as a treatment of ARPKD.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Role of CFTR in Autosomal Dominant Polycystic Kidney Disease (Exhibit Hall, Orange County Convention Center, West Building) -  Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_1144;    
    We showed that the CFTR corrector, VX-809 relocates CFTR to the basolateral membrane creating an absorptive phenotype...Finally, we determined, if PC2’s location in the primary cilium is altered in CFTR-null mice and found that the colocalization is decreased in CFTR-null mice. Conclusion These data suggest that CFTR does play a role in cilia both in impacting its length and the location of PC2.
  • ||||||||||  Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex
    Lipid-based therapeutic strategies in addition to cystic fibrosis transmembrane conductance regulator modulators for cystic fibrosis treatment (Exhibition Hall) -  Oct 8, 2022 - Abstract #NACFC2022NACFC_1216;    
    Background:Combined therapy with modulators, based on correctors andpotentiators, is considered mandatory to efficiently rescue F508del –cystic fibrosis (CF) transmembrane conductance regulator (CFTR), but co-presence of different small organic molecules interacting with F508del-CFTR may decrease the efficiency of mutant protein rescue, as shown in thecase of the negative effect produced by the potentiator ivacaftor whenassociated with the corrector lumacaftor [1]...Because CFTR stability and function are the resultof coordination of a molecular complex composed of lipids and proteins,we sought to investigate the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on lipid microenvironment surrounding the CFTR...Taken together, these results suggest that GM1 and itspharmacological derivative LIGA20 play a critical role in stabilization ofCFTR at the plasma membrane, also in the presence of infection. Theassociation between these sphingolipids and current therapeutic treat-ments could increase the efficacy of CFTR modulators.
  • ||||||||||  Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex
    Personalized medicine approaches directed at rare cystic fibrosis transmembrane conductance regulator trafficking mutations contribute to elucidation of correction mechanisms (Exhibition Hall) -  Oct 8, 2022 - Abstract #NACFC2022NACFC_1207;    
    We also aimed to determine whether mutation location wouldsomehow influence or predict the response to the correctors.We produced novel CF bronchial epitheliel (CFBE)-based celllines stably expressing 15 CFTR variants (P5L, R75G, H139R, I148 T, D192G,G194R, H199Y, V201M, P205S, W361R, A550 T, L558S, L571S, S945L,M1137R) and used them to assess CFTR expression and maturation bywestern blot after treatment with correctors (VX-809, VX-661, VX-445, andthe double corrector combination VX-661 + VX-445). Our study confirms the relevance of assessing the response ofrare mutations to HEMTs (in a personalized medicine approach, that is bestachieved by combining data from cellular and patient-derived models) andsuggest the existence of a location-dependent pattern of response tomodulators that may help clarify the mechanism of action of correctors.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Robust, efficient workflow to establish, culture, and functionally assess primary-isolated airway epithelial cells (Exhibition Hall) -  Oct 8, 2022 - Abstract #NACFC2022NACFC_1052;    
    These airway organoids were thentreated with CFTR corrector VX-809 for 24 hours, followed by 6-hourtreatment with amiloride, forskolin, and genistein to induce organoidswelling.Our results demonstrate that ALI cultures derived from CF donorsdisplayed partial rescue of CFTR across multiple passages after treatmentwith VX-809. In summary, the PneumaCult workflow supports robust,efficient culture of primary-airway epithelial cells that can be used asphysiologically relevant models suitable for CF research, CFTR correctorscreening, and studying airway biology.