PMID-sentid Pub_year Sent_text compound_name comp_offset prot_official_name organism prot_offset 34054511-3 2021 HE4 protein levels were measured in the supernatants of CFBE 41o- cells expressing F508del-CFTR or wild-type CFTR (wt-CFTR) after administration of lumacaftor/ivacaftor or tezacaftor/ivacaftor, while HE4 expression in CFBE 41o- cells were also analyzed following application of adenylate cyclase activators Forskolin/IBMX or CFTRinh172. lumacaftor 148-158 WAP four-disulfide core domain 2 Homo sapiens 0-3 34020896-6 2021 For both heterologously expressed and native F508del-CFTR rescued by either VX-809 or C18, the magnitude of CFTR-mediated Cl- currents was dependent on the presence of extracellular phosphate. lumacaftor 76-82 CF transmembrane conductance regulator Homo sapiens 53-57 34020896-6 2021 For both heterologously expressed and native F508del-CFTR rescued by either VX-809 or C18, the magnitude of CFTR-mediated Cl- currents was dependent on the presence of extracellular phosphate. lumacaftor 76-82 CF transmembrane conductance regulator Homo sapiens 108-112 33616476-2 2021 CFTR corrector, lumacaftor and the potentiator ivacaftor improve CFTR function with terminal PTC mutations, and enhance the effect of readthrough agents. lumacaftor 16-26 CF transmembrane conductance regulator Homo sapiens 65-69 33965000-1 2021 BACKGROUND: A previous phase 3 study showed that lumacaftor-ivacaftor was generally safe and well tolerated over 24 weeks of treatment in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation. lumacaftor 49-59 CF transmembrane conductance regulator Homo sapiens 210-214 33965000-21 2021 These findings support the use of lumacaftor-ivacaftor for up to 120 weeks in young children with cystic fibrosis aged 2 years and older homozygous for the F508del-CFTR mutation. lumacaftor 34-44 CF transmembrane conductance regulator Homo sapiens 164-168 32644818-0 2021 Clinical Effectiveness of Lumacaftor/Ivacaftor in Cystic Fibrosis Patients Homozygous for F508del-CFTR. lumacaftor 26-36 CF transmembrane conductance regulator Homo sapiens 98-102 33534640-7 2021 In contrast, the stabilization of intermediates with the modulator VX-809 promotes the association of N1303K-CFTR with autophagy initiation machinery. lumacaftor 67-73 CF transmembrane conductance regulator Homo sapiens 109-113 33781744-2 2021 This rare mutation (reported in <300 patients worldwide) responds robustly to CFTR correctors such as lumacaftor and tezacaftor, with rescue in model systems that far exceeds what can be achieved for the archetypical CFTR mutant F508del. lumacaftor 102-112 CF transmembrane conductance regulator Homo sapiens 78-82 33781744-2 2021 This rare mutation (reported in <300 patients worldwide) responds robustly to CFTR correctors such as lumacaftor and tezacaftor, with rescue in model systems that far exceeds what can be achieved for the archetypical CFTR mutant F508del. lumacaftor 102-112 CF transmembrane conductance regulator Homo sapiens 217-221 32586736-1 2021 BACKGROUND: Increased rates of respiratory adverse events have been observed in people >=12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV1) of <40%. lumacaftor 182-192 CF transmembrane conductance regulator Homo sapiens 155-159 33516285-1 2021 BACKGROUND: The safety and efficacy of 24 weeks of lumacaftor-ivacaftor combination therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation was previously shown in two phase 3 studies. lumacaftor 51-61 CF transmembrane conductance regulator Homo sapiens 168-172 33516285-16 2021 INTERPRETATION: Lumacaftor-ivacaftor therapy in children homozygous for F508del-CFTR who initiated treatment at age 6-11 years was generally safe and well tolerated, and efficacy was sustained for up to 120 weeks. lumacaftor 16-26 CF transmembrane conductance regulator Homo sapiens 80-84 33516285-17 2021 These data support the long-term use of lumacaftor-ivacaftor to treat children aged 6 years and older who are homozygous for the F508del-CFTR mutation. lumacaftor 40-50 CF transmembrane conductance regulator Homo sapiens 137-141 33399458-2 2021 With the discovery of Ivacaftor and Lumacaftor, it has been shown that administration of one or more small molecules can partially restore the CFTR function. lumacaftor 36-46 CF transmembrane conductance regulator Homo sapiens 143-147 33600745-1 2021 RATIONALE: Previous studies showed that lumacaftor-ivacaftor therapy results in partial rescue of cystic fibrosis transmembrane conductance regulator (CFTR) activity and moderate improvement of spirometry in Phe508del homozygous patients with cystic fibrosis (CF). lumacaftor 40-50 CF transmembrane conductance regulator Homo sapiens 98-149 33600745-1 2021 RATIONALE: Previous studies showed that lumacaftor-ivacaftor therapy results in partial rescue of cystic fibrosis transmembrane conductance regulator (CFTR) activity and moderate improvement of spirometry in Phe508del homozygous patients with cystic fibrosis (CF). lumacaftor 40-50 CF transmembrane conductance regulator Homo sapiens 151-155 33586024-1 2021 PURPOSE: The question whether the new cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs aimed at restoring CFTR protein function might improve glucose metabolism is gaining attention, but data on the effect of lumacaftor/ivacaftor treatment (LUMA/IVA) on glucose tolerance are limited. lumacaftor 235-245 CF transmembrane conductance regulator Homo sapiens 91-95 32526307-0 2021 Drug allergy to CFTR modulator therapy associated with lumacaftor-specific CD4+ T lymphocytes. lumacaftor 55-65 CF transmembrane conductance regulator Homo sapiens 16-20 32526307-0 2021 Drug allergy to CFTR modulator therapy associated with lumacaftor-specific CD4+ T lymphocytes. lumacaftor 55-65 CD4 molecule Homo sapiens 75-78 32762058-1 2021 Ivacaftor (IVA) and lumacaftor (LUM) modulate the cystic fibrosis (CF) transmembrane conductance regulator protein. lumacaftor 20-30 CF transmembrane conductance regulator Homo sapiens 50-106 32762058-1 2021 Ivacaftor (IVA) and lumacaftor (LUM) modulate the cystic fibrosis (CF) transmembrane conductance regulator protein. lumacaftor 32-35 CF transmembrane conductance regulator Homo sapiens 50-106 32644818-1 2021 RATIONALE: The combination of lumacaftor and ivacaftor (LUM/IVA) is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment for homozygous F508del CF patients. lumacaftor 30-40 CF transmembrane conductance regulator Homo sapiens 80-131 32644818-1 2021 RATIONALE: The combination of lumacaftor and ivacaftor (LUM/IVA) is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment for homozygous F508del CF patients. lumacaftor 30-40 CF transmembrane conductance regulator Homo sapiens 133-137 33520477-5 2020 The introduction and approval of CFTR modulators-lumacaftor (LUM) and ivacaftor (IVA) in 2015 by the US Food and Drug Administration (FDA) reduced the mortality and morbidity rates associated with the disease. lumacaftor 49-59 CF transmembrane conductance regulator Homo sapiens 33-37 32741662-2 2021 Corrector compounds like lumacaftor partially rescue the processing defect of F508del-CFTR whereas potentiators like ivacaftor, enhance its channel activity once trafficked to the cell surface. lumacaftor 25-35 CF transmembrane conductance regulator Homo sapiens 86-90 33313305-10 2020 BI 1265162 alone and in combination with CF transmembrane conductance regulator (CFTR) modulators decreased water transport and increased MCC in both normal and CF airway human epithelial models and also increased the effects of CFTR modulators in CF epithelium to reach the effect size seen in healthy epithelium with ivacaftor/lumacaftor alone. lumacaftor 329-339 CF transmembrane conductance regulator Homo sapiens 41-79 33358691-2 2021 METHODS: We conducted a multisite Phase 4 trial comparing the impact of lumacaftor/ivacaftor on exercise tolerance with that of placebo in participants >= 12 years of age with CF homozygous for F508del-CFTR. lumacaftor 72-82 CF transmembrane conductance regulator Homo sapiens 202-206 32971410-0 2020 Discovery of novel VX-809 hybrid derivatives as F508del-CFTR correctors by molecular modeling, chemical synthesis and biological assays. lumacaftor 19-25 CF transmembrane conductance regulator Homo sapiens 56-60 33313305-10 2020 BI 1265162 alone and in combination with CF transmembrane conductance regulator (CFTR) modulators decreased water transport and increased MCC in both normal and CF airway human epithelial models and also increased the effects of CFTR modulators in CF epithelium to reach the effect size seen in healthy epithelium with ivacaftor/lumacaftor alone. lumacaftor 329-339 CF transmembrane conductance regulator Homo sapiens 81-85 33239626-10 2020 Finally, we found that C18, an analog of the CFTR corrector compound Lumacaftor, induces almost no transcriptional perturbation despite its rescue activity. lumacaftor 69-79 CF transmembrane conductance regulator Homo sapiens 45-49 32687398-0 2020 Comparison of Organoid Swelling and In Vivo Biomarkers of CFTR Function to Determine Effects of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation. lumacaftor 96-106 CF transmembrane conductance regulator Homo sapiens 58-62 32740537-2 2020 While Lumacaftor/Ivacaftor is well-known to modulate the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein in lungs, no data are available on the impact of this treatment on CF intestinal disorders. lumacaftor 6-16 CF transmembrane conductance regulator Homo sapiens 67-118 32740537-2 2020 While Lumacaftor/Ivacaftor is well-known to modulate the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein in lungs, no data are available on the impact of this treatment on CF intestinal disorders. lumacaftor 6-16 CF transmembrane conductance regulator Homo sapiens 120-124 32734574-2 2020 Here, a simulation study predicted ivacaftor, tezacaftor, and elexacaftor exposures and impacts on CFTR modulation following transition from ivacaftor [a cytochrome P450 3A (CYP3A) substrate], lumacaftor (a CYP3A inducer)/ivacaftor, or tezacaftor/ivacaftor to TC. lumacaftor 193-203 CF transmembrane conductance regulator Homo sapiens 99-103 32734574-4 2020 PBPK models were parameterized using data from human hepatocytes to account for CYP3A induction by lumacaftor and validated to match clinical data from healthy volunteers and pwCF. lumacaftor 99-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-85 32734574-9 2020 Lumacaftor-mediated CYP3A induction resolved within approximately 2 weeks. lumacaftor 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 20-25 33249003-0 2021 Lumacaftor/ivacaftor in people with cystic fibrosis with an A455E-CFTR mutation. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 66-70 33249003-1 2021 BACKGROUND: Previous in vitro organoid data showed A455E-CFTR, a rare CFTR mutation with 4.1% prevalence in the Netherlands, responds to lumacaftor/ivacaftor (LUM/IVA). lumacaftor 137-147 CF transmembrane conductance regulator Homo sapiens 57-61 33249003-1 2021 BACKGROUND: Previous in vitro organoid data showed A455E-CFTR, a rare CFTR mutation with 4.1% prevalence in the Netherlands, responds to lumacaftor/ivacaftor (LUM/IVA). lumacaftor 137-147 CF transmembrane conductance regulator Homo sapiens 70-74 32940533-3 2020 Recently, FDA-approved cystic fibrosis protein trafficking chaperone, lumacaftor (LUM), has been proposed as novel therapy for LQT2. lumacaftor 70-80 potassium voltage-gated channel subfamily H member 2 Homo sapiens 127-131 33009446-7 2020 In order to rescue the function of the mutated V2R, we tested VX-809, sildenafil citrate, ibuprofen and tolvaptan in MDCK cells. lumacaftor 62-68 arginine vasopressin receptor 2 Canis lupus familiaris 47-50 33165217-1 2021 BACKGROUND: The novel cystic fibrosis transmembrane conductance receptor (CFTR) modulators, ivacaftor, lumacaftor, and tezacaftor, are the first drugs directly targeting the underlying pathophysiological mechanism in cystic fibrosis (CF); however, independent studies describing their pharmacokinetics (PK) are lacking. lumacaftor 103-113 CF transmembrane conductance regulator Homo sapiens 22-72 33165217-1 2021 BACKGROUND: The novel cystic fibrosis transmembrane conductance receptor (CFTR) modulators, ivacaftor, lumacaftor, and tezacaftor, are the first drugs directly targeting the underlying pathophysiological mechanism in cystic fibrosis (CF); however, independent studies describing their pharmacokinetics (PK) are lacking. lumacaftor 103-113 CF transmembrane conductance regulator Homo sapiens 74-78 32940533-3 2020 Recently, FDA-approved cystic fibrosis protein trafficking chaperone, lumacaftor (LUM), has been proposed as novel therapy for LQT2. lumacaftor 82-85 potassium voltage-gated channel subfamily H member 2 Homo sapiens 127-131 32940533-4 2020 Here, we test the efficacy of LUM treatment in patient-specific induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) derived from two patients with known LQT2 trafficking defective mutations and a patient with novel KCNH2 variant, p.R685P. lumacaftor 30-33 potassium voltage-gated channel subfamily H member 2 Homo sapiens 157-161 32940533-4 2020 Here, we test the efficacy of LUM treatment in patient-specific induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) derived from two patients with known LQT2 trafficking defective mutations and a patient with novel KCNH2 variant, p.R685P. lumacaftor 30-33 potassium voltage-gated channel subfamily H member 2 Homo sapiens 219-224 32940533-10 2020 While LUM treatment rescued the phenotype of KCNH2-N633S and KCNH2-R685P, LUM paradoxically prolonged the APD90 in KCNH2-G604S iPSC-CMs. lumacaftor 6-9 potassium voltage-gated channel subfamily H member 2 Homo sapiens 45-50 32940533-10 2020 While LUM treatment rescued the phenotype of KCNH2-N633S and KCNH2-R685P, LUM paradoxically prolonged the APD90 in KCNH2-G604S iPSC-CMs. lumacaftor 6-9 potassium voltage-gated channel subfamily H member 2 Homo sapiens 61-66 32940533-10 2020 While LUM treatment rescued the phenotype of KCNH2-N633S and KCNH2-R685P, LUM paradoxically prolonged the APD90 in KCNH2-G604S iPSC-CMs. lumacaftor 6-9 potassium voltage-gated channel subfamily H member 2 Homo sapiens 61-66 31848044-1 2020 BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) improves outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1 > 40%. lumacaftor 12-22 lumican Homo sapiens 34-37 33014932-8 2020 The CFTR correctors VX-809 (lumacaftor) and VX-661 (tezacaftor) significantly increased CFTR currents for F508del/R117H to 73 and 67% WT, respectively. lumacaftor 28-38 CF transmembrane conductance regulator Homo sapiens 4-8 33014932-8 2020 The CFTR correctors VX-809 (lumacaftor) and VX-661 (tezacaftor) significantly increased CFTR currents for F508del/R117H to 73 and 67% WT, respectively. lumacaftor 28-38 CF transmembrane conductance regulator Homo sapiens 88-92 32807895-9 2020 Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction. lumacaftor 36-46 surface glycoprotein Severe acute respiratory syndrome coronavirus 2 87-92 32807895-9 2020 Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction. lumacaftor 36-46 angiotensin converting enzyme 2 Homo sapiens 132-136 32290721-3 2020 The discovery through in vitro studies of the CFTR correctors (i.e. lumacaftor, tezacaftor) that partially rescue the misprocessing of F508del-CFTR with the potentiator ivacaftor is promising in giving an unprecedented clinical benefit in affected patients.Areas covered: Online databases were searched using key phrases for CF and CFTR modulators. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 46-50 32290721-3 2020 The discovery through in vitro studies of the CFTR correctors (i.e. lumacaftor, tezacaftor) that partially rescue the misprocessing of F508del-CFTR with the potentiator ivacaftor is promising in giving an unprecedented clinical benefit in affected patients.Areas covered: Online databases were searched using key phrases for CF and CFTR modulators. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 143-147 32290721-3 2020 The discovery through in vitro studies of the CFTR correctors (i.e. lumacaftor, tezacaftor) that partially rescue the misprocessing of F508del-CFTR with the potentiator ivacaftor is promising in giving an unprecedented clinical benefit in affected patients.Areas covered: Online databases were searched using key phrases for CF and CFTR modulators. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 143-147 32487229-1 2020 RATIONALE: Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms. lumacaftor 11-21 lumican Homo sapiens 33-36 32703846-3 2020 For CF patients and CF mice, we developed a HCO3 - drinking test to assess the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in urinary HCO3 -excretion and applied it in the patients before and after treatment with the novel CFTR modulator drug, lumacaftor-ivacaftor. lumacaftor 271-281 cystic fibrosis transmembrane conductance regulator Mus musculus 91-142 32703846-3 2020 For CF patients and CF mice, we developed a HCO3 - drinking test to assess the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in urinary HCO3 -excretion and applied it in the patients before and after treatment with the novel CFTR modulator drug, lumacaftor-ivacaftor. lumacaftor 271-281 cystic fibrosis transmembrane conductance regulator Mus musculus 144-148 32703846-9 2020 In patients, treatment with the CFTR modulator drug lumacaftor-ivacaftor increased the renal ability to excrete HCO3 -. lumacaftor 52-62 CF transmembrane conductance regulator Homo sapiens 32-36 31924546-1 2020 OBJECTIVE: The first available CFTR modulator combination for homozygous F508del patients, lumacaftor/ivacaftor, has not been tested in patients with percentage predicted (pp)FEV1 > 90 in the phase III trials. lumacaftor 91-101 CF transmembrane conductance regulator Homo sapiens 31-35 31902692-1 2020 BACKGROUND: Lumacaftor-ivacaftor combination is a promising treatment for cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 131-135 31902692-10 2020 CONCLUSIONS: Considering the medico-economic impact of CFTR modulator therapy, high adherence rates to lumacaftor-ivacaftor found in this study are encouraging. lumacaftor 103-113 CF transmembrane conductance regulator Homo sapiens 55-59 32244302-0 2020 Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi ) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells. lumacaftor 66-76 CF transmembrane conductance regulator Homo sapiens 117-121 31601120-1 2020 Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (>=12 yr) and adults (>=18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. lumacaftor 11-21 CF transmembrane conductance regulator Homo sapiens 37-41 31474496-3 2020 Lumacaftor/ivacaftor is a CFTR modulator approved for patients homozygous for the CFTR variant p.Phe508del, but there are wide variations in treatment responses preventing prediction of patient responses. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 26-30 31474496-3 2020 Lumacaftor/ivacaftor is a CFTR modulator approved for patients homozygous for the CFTR variant p.Phe508del, but there are wide variations in treatment responses preventing prediction of patient responses. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 82-86 31594690-11 2020 Lower exposures of GLPG2737 (and active metabolite M4) were observed than would be expected if administered alone (as lumacaftor induces CYP3A4). lumacaftor 118-128 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 137-143 32256364-6 2020 Importantly, W361R-CFTR also responded well to CFTR modulators: its maturation defect was efficiently corrected by VX-809 treatment and its channel activity further potentiated by VX-770. lumacaftor 115-121 CF transmembrane conductance regulator Homo sapiens 19-23 32256364-6 2020 Importantly, W361R-CFTR also responded well to CFTR modulators: its maturation defect was efficiently corrected by VX-809 treatment and its channel activity further potentiated by VX-770. lumacaftor 115-121 CF transmembrane conductance regulator Homo sapiens 47-51 32118580-4 2020 In vitro application of ivacaftor/lumacaftor or ivacaftor/tezacaftor to CF monocytes showed a significant reduction in IL-18, whereas IL-1beta was only reduced with ivacaftor/tezacaftor. lumacaftor 34-44 interleukin 18 Homo sapiens 119-124 32092967-2 2020 ORKAMBI (Lumacaftor-Ivacaftor) is an approved combination therapy for Cystic Fibrosis (CF) patients bearing the most common mutation, F508del, in the cystic fibrosis conductance regulator (CFTR) protein. lumacaftor 10-20 CF transmembrane conductance regulator Homo sapiens 151-188 32092967-2 2020 ORKAMBI (Lumacaftor-Ivacaftor) is an approved combination therapy for Cystic Fibrosis (CF) patients bearing the most common mutation, F508del, in the cystic fibrosis conductance regulator (CFTR) protein. lumacaftor 10-20 CF transmembrane conductance regulator Homo sapiens 190-194 32128363-3 2020 An interview with Ana (pseudonym), who became pregnant twice while taking the medication lumacaftor/ivacaftor (LUMA/IVA), was analyzed using thematic analysis. lumacaftor 89-99 transmembrane protein 43 Homo sapiens 111-115 31601120-1 2020 Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (>=12 yr) and adults (>=18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. lumacaftor 11-21 CF transmembrane conductance regulator Homo sapiens 43-94 31189070-9 2019 l-arginine uptake via SLC6A14 augmented F508del-CFTR function at baseline and after treatment with lumacaftor. lumacaftor 99-109 solute carrier family 6 member 14 Homo sapiens 22-29 31966908-24 2019 CONCLUSION: Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. lumacaftor 38-48 CF transmembrane conductance regulator Homo sapiens 23-27 31189070-9 2019 l-arginine uptake via SLC6A14 augmented F508del-CFTR function at baseline and after treatment with lumacaftor. lumacaftor 99-109 CF transmembrane conductance regulator Homo sapiens 48-52 31006073-1 2019 INTRODUCTION: A new class of drugs in the treatment of cystic fibrosis (CF) includes two agents: lumacaftor, which corrects CFTR channel protein, and ivacaftor, which increases CFTR channel activity. lumacaftor 97-107 CF transmembrane conductance regulator Homo sapiens 124-128 31450978-3 2019 CK19 overexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine residue at position 508) at the plasma membrane (PM), promoting Cl- secretion across human bronchial epithelial (HBE) cells. lumacaftor 60-70 keratin 19 Homo sapiens 0-4 31450978-3 2019 CK19 overexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine residue at position 508) at the plasma membrane (PM), promoting Cl- secretion across human bronchial epithelial (HBE) cells. lumacaftor 60-70 CF transmembrane conductance regulator Homo sapiens 96-100 31450978-3 2019 CK19 overexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine residue at position 508) at the plasma membrane (PM), promoting Cl- secretion across human bronchial epithelial (HBE) cells. lumacaftor 72-78 keratin 19 Homo sapiens 0-4 31450978-3 2019 CK19 overexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine residue at position 508) at the plasma membrane (PM), promoting Cl- secretion across human bronchial epithelial (HBE) cells. lumacaftor 72-78 CF transmembrane conductance regulator Homo sapiens 96-100 32259083-3 2020 The discovery and development of the CFTR potentiator ivacaftor was a major break-through in CF therapy and has triggered an enormous incentive for seeking effective modulators such as lumacaftor, tezacaftor or elexacaftor for all patients with CF. lumacaftor 185-195 CF transmembrane conductance regulator Homo sapiens 37-41 31427400-7 2019 SIGNIFICANCE STATEMENT: These proof-of-concept studies highlight the potential to boost the response to cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, lumacaftor and ivacaftor, in patient-derived airway tissues expressing the major CF-causing mutant, F508del-CFTR, by enhancing other regulatory pathways. lumacaftor 180-190 CF transmembrane conductance regulator Homo sapiens 104-160 30738802-0 2019 Lumacaftor-rescued F508del-CFTR has a modified bicarbonate permeability. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 27-31 30738802-3 2019 We studied the permeability properties of the CFTR mutant F508del treated with the corrector lumacaftor, showing that the rescued protein has selectivity properties different than the wild type CFTR, showing an augmented bicarbonate permeability. lumacaftor 93-103 CF transmembrane conductance regulator Homo sapiens 46-50 30738802-3 2019 We studied the permeability properties of the CFTR mutant F508del treated with the corrector lumacaftor, showing that the rescued protein has selectivity properties different than the wild type CFTR, showing an augmented bicarbonate permeability. lumacaftor 93-103 CF transmembrane conductance regulator Homo sapiens 194-198 31409974-5 2019 Lumacaftor, the corrector, works by increasing the trafficking of CFTR proteins to the outer cell membrane. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 66-70 31456498-1 2019 BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) is indicated for patients with cystic fibrosis (CF) homozygous for the F508del mutation in the CFTR gene. lumacaftor 12-22 lumican Homo sapiens 34-37 31456498-1 2019 BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) is indicated for patients with cystic fibrosis (CF) homozygous for the F508del mutation in the CFTR gene. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 138-142 31012285-1 2019 BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor and lumacaftor/ivacaftor improve the status of existing infections in patients with cystic fibrosis (CF). lumacaftor 100-110 CF transmembrane conductance regulator Homo sapiens 16-67 31012285-1 2019 BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor and lumacaftor/ivacaftor improve the status of existing infections in patients with cystic fibrosis (CF). lumacaftor 100-110 CF transmembrane conductance regulator Homo sapiens 69-73 31409974-7 2019 In vivo lumacaftor-ivacaftor improves Phe508del-CFTR activity in airways, sweat ducts and intestine to approximately 10-20% of normal CFTR function with greater reductions in sweat chloride levels in children versus adults. lumacaftor 8-18 CF transmembrane conductance regulator Homo sapiens 48-52 31409974-7 2019 In vivo lumacaftor-ivacaftor improves Phe508del-CFTR activity in airways, sweat ducts and intestine to approximately 10-20% of normal CFTR function with greater reductions in sweat chloride levels in children versus adults. lumacaftor 8-18 CF transmembrane conductance regulator Homo sapiens 134-138 31218221-4 2019 Combinations of CFTR correctors and potentiators (i.e. lumacaftor/ivacaftor, tezacaftor/ivacaftor) have demonstrated clinical benefit in subsets of patients. lumacaftor 55-65 CF transmembrane conductance regulator Homo sapiens 16-20 31117414-4 2019 Samples from patients undergoing treatment with CFTR modulators including ivacaftor, lumacaftor, and tezacaftor showed a high normalized peak in response to therapy. lumacaftor 85-95 CF transmembrane conductance regulator Homo sapiens 48-52 31227724-4 2019 As proof-of-concept, differentiated human iLEC harboring the Cystic Fibrosis mutation dF508 demonstrated pharmacological rescue of CFTR function using the combination of lumacaftor and ivacaftor. lumacaftor 170-180 CF transmembrane conductance regulator Homo sapiens 131-135 30358440-2 2019 Herein, we tested the hypothesis that a reduction of the cholesterol content of CF human airway epithelial cells by cyclodextrins reduces the inhibitory effect of OMVs on VX-809 (lumacaftor)-stimulated Phe508del CFTR Cl- secretion. lumacaftor 179-189 CF transmembrane conductance regulator Homo sapiens 212-216 30686767-1 2019 BACKGROUND: The efficacy, safety, and tolerability of lumacaftor and ivacaftor are established in patients aged 6 years and older with cystic fibrosis, homozygous for the F508del-CFTR mutation. lumacaftor 54-64 CF transmembrane conductance regulator Homo sapiens 179-183 30997048-1 2019 We report the initiation of CFTR modulator lumacaftor/ivacaftor combination (LUM/IVA) in two adolescents with cystic fibrosis who were treated with antifungal azoles (AZO) and tacrolimus (TCS) for liver transplantation. lumacaftor 43-53 CF transmembrane conductance regulator Homo sapiens 28-32 30997048-1 2019 We report the initiation of CFTR modulator lumacaftor/ivacaftor combination (LUM/IVA) in two adolescents with cystic fibrosis who were treated with antifungal azoles (AZO) and tacrolimus (TCS) for liver transplantation. lumacaftor 43-53 lumican Homo sapiens 77-80 30753398-1 2019 AIMS: Having shown that Lumacaftor rescued the hERG trafficking defect in the induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two LQT2 patients, we tested whether the commercial association Lumacaftor + Ivacaftor (LUM + IVA) could shorten the QTc in the same two patients. lumacaftor 24-34 ETS transcription factor ERG Homo sapiens 47-51 30753398-4 2019 Lumacaftor + Ivacaftor shortened QTc significantly in both patients: in V6 from 551 +- 22 ms to 523 +- 35 ms in Patient 1 (Pt1) and from 472 +- 21 ms to 449 +- 20 ms in Patient 2 (Pt2); in DII from 562 +- 25 ms to 549 +- 35 ms in Pt1 and from 485 +- 32 ms to 452 +- 18 ms in Pt2. lumacaftor 0-10 zinc finger protein 77 Homo sapiens 123-126 30753398-4 2019 Lumacaftor + Ivacaftor shortened QTc significantly in both patients: in V6 from 551 +- 22 ms to 523 +- 35 ms in Patient 1 (Pt1) and from 472 +- 21 ms to 449 +- 20 ms in Patient 2 (Pt2); in DII from 562 +- 25 ms to 549 +- 35 ms in Pt1 and from 485 +- 32 ms to 452 +- 18 ms in Pt2. lumacaftor 0-10 zinc finger protein 77 Homo sapiens 230-233 30595473-1 2019 BACKGROUND: Ivacaftor-lumacaftor combination therapy corrects the F508 del-CFTR mutated protein which causes Cystic Fibrosis. lumacaftor 22-32 CF transmembrane conductance regulator Homo sapiens 75-79 30595473-12 2019 The F87L-I1027T-F508del-CFTR complex allele abolished the lumacaftor corrector effect. lumacaftor 58-68 CF transmembrane conductance regulator Homo sapiens 24-28 30677435-4 2019 While lumacaftor is used to correct p.Phe508del mutation (the loss of phenylalanine at position 508) and increase the amount of cell surface-localized CFTR protein, ivacaftor serves as a CFTR potentiator that increases the open probability of CFTR channels. lumacaftor 6-16 CF transmembrane conductance regulator Homo sapiens 151-155 30358440-2 2019 Herein, we tested the hypothesis that a reduction of the cholesterol content of CF human airway epithelial cells by cyclodextrins reduces the inhibitory effect of OMVs on VX-809 (lumacaftor)-stimulated Phe508del CFTR Cl- secretion. lumacaftor 171-177 CF transmembrane conductance regulator Homo sapiens 212-216 30358440-5 2019 Both cyclodextrins reduced OMV inhibition of VX-809-stimulated Phe508del-CFTR Cl- secretion when added to the apical side of CF monolayers. lumacaftor 45-51 CF transmembrane conductance regulator Homo sapiens 73-77 30146268-1 2019 BACKGROUND: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. lumacaftor 94-104 lumican Homo sapiens 116-119 31403270-0 2019 The CFTR Corrector, VX-809 (Lumacaftor), Rescues ABCA4 Trafficking Mutants: a Potential Treatment for Stargardt Disease. lumacaftor 20-26 CF transmembrane conductance regulator Homo sapiens 4-8 31403270-0 2019 The CFTR Corrector, VX-809 (Lumacaftor), Rescues ABCA4 Trafficking Mutants: a Potential Treatment for Stargardt Disease. lumacaftor 20-26 ATP binding cassette subfamily A member 4 Homo sapiens 49-54 31403270-0 2019 The CFTR Corrector, VX-809 (Lumacaftor), Rescues ABCA4 Trafficking Mutants: a Potential Treatment for Stargardt Disease. lumacaftor 28-38 CF transmembrane conductance regulator Homo sapiens 4-8 31403270-0 2019 The CFTR Corrector, VX-809 (Lumacaftor), Rescues ABCA4 Trafficking Mutants: a Potential Treatment for Stargardt Disease. lumacaftor 28-38 ATP binding cassette subfamily A member 4 Homo sapiens 49-54 30268148-2 2018 The objective of this study was to assess the cost-effectiveness of lumacaftor/ivacaftor combination for the treatment of CF homozygous for F508del CF Transmembrane Conductance Regulator (CFTR) mutation. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 148-186 30803355-0 2019 Modeling long-term health outcomes of patients with cystic fibrosis homozygous for F508del-CFTR treated with lumacaftor/ivacaftor. lumacaftor 109-119 CF transmembrane conductance regulator Homo sapiens 91-95 30803355-1 2019 BACKGROUND: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 145-191 30803355-1 2019 BACKGROUND: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 193-197 30803355-2 2019 However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. lumacaftor 40-50 lumican Homo sapiens 62-65 30540818-0 2018 Corticosteroid use and increased CXCR2 levels on leukocytes are associated with lumacaftor/ivacaftor discontinuation in cystic fibrosis patients homozygous for the F508del CFTR mutation. lumacaftor 80-90 C-X-C motif chemokine receptor 2 Homo sapiens 33-38 30540818-3 2018 The combination therapeutic lumacaftor/ivacaftor (Orkambi, luma/iva) partially corrects folding and potentiates CFTR function impaired by the F508del mutation. lumacaftor 28-38 CF transmembrane conductance regulator Homo sapiens 112-116 30459435-6 2018 CFTR expression increased and apoptosis decreased in response to ivacaftor or lumacaftor/ivacaftor therapy, and phagocytosis improved with ivacaftor alone. lumacaftor 78-88 CF transmembrane conductance regulator Homo sapiens 0-4 30268148-2 2018 The objective of this study was to assess the cost-effectiveness of lumacaftor/ivacaftor combination for the treatment of CF homozygous for F508del CF Transmembrane Conductance Regulator (CFTR) mutation. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 188-192 29327948-0 2018 Effects of Lumacaftor-Ivacaftor Therapy on Cystic Fibrosis Transmembrane Conductance Regulator Function in Phe508del Homozygous Patients with Cystic Fibrosis. lumacaftor 11-21 CF transmembrane conductance regulator Homo sapiens 43-94 29903751-2 2018 Recently, ORKAMBI, a combination therapy that includes a corrector of the processing defect of F508del-CFTR (lumacaftor or VX-809) and a potentiator of channel activity (ivacaftor or VX-770), was approved for CF patients homozygous for this mutation. lumacaftor 109-119 CF transmembrane conductance regulator Homo sapiens 103-107 30061653-1 2018 Pharmacological chaperones (e.g. VX-809, lumacaftor) that bind directly to F508del-CFTR and correct its mislocalization are promising therapeutics for Cystic Fibrosis (CF). lumacaftor 33-39 CF transmembrane conductance regulator Homo sapiens 83-87 30061653-1 2018 Pharmacological chaperones (e.g. VX-809, lumacaftor) that bind directly to F508del-CFTR and correct its mislocalization are promising therapeutics for Cystic Fibrosis (CF). lumacaftor 41-51 CF transmembrane conductance regulator Homo sapiens 83-87 29875161-3 2018 Here, we demonstrate a role for VX-809, a corrector of cystic fibrosis transmembrane conductance regulator (CFTR), conventionally used to manage cystic fibrosis in reducing renal cyst growth. lumacaftor 32-38 cystic fibrosis transmembrane conductance regulator Mus musculus 55-106 29875161-3 2018 Here, we demonstrate a role for VX-809, a corrector of cystic fibrosis transmembrane conductance regulator (CFTR), conventionally used to manage cystic fibrosis in reducing renal cyst growth. lumacaftor 32-38 cystic fibrosis transmembrane conductance regulator Mus musculus 108-112 29875161-4 2018 VX-809 reduced cyst growth in Pkd1-knockout mice and in proximal, tubule-derived, cultured Pkd1 knockout cells. lumacaftor 0-6 polycystin 1, transient receptor potential channel interacting Mus musculus 30-34 29875161-4 2018 VX-809 reduced cyst growth in Pkd1-knockout mice and in proximal, tubule-derived, cultured Pkd1 knockout cells. lumacaftor 0-6 polycystin 1, transient receptor potential channel interacting Mus musculus 91-95 29875161-5 2018 VX-809 reduced both basal and forskolin-activated cAMP levels and also decreased the expression of the adenylyl cyclase AC3 but not of AC6. lumacaftor 0-6 adenylate cyclase 3 Mus musculus 120-123 29875161-5 2018 VX-809 reduced both basal and forskolin-activated cAMP levels and also decreased the expression of the adenylyl cyclase AC3 but not of AC6. lumacaftor 0-6 adenylate cyclase 6 Mus musculus 135-138 29875161-9 2018 Moreover, VX-809 strongly decreased an ER stress marker, the GADD153 protein, and cell proliferation but had only a small effect on apoptosis. lumacaftor 10-16 DNA-damage inducible transcript 3 Mus musculus 61-68 30046002-3 2018 The magnitude of drug response was highly correlated with residual CFTR function for the potentiator ivacaftor, the corrector lumacaftor, and ivacaftor-lumacaftor combination therapy. lumacaftor 126-136 CF transmembrane conductance regulator Homo sapiens 67-71 30046002-3 2018 The magnitude of drug response was highly correlated with residual CFTR function for the potentiator ivacaftor, the corrector lumacaftor, and ivacaftor-lumacaftor combination therapy. lumacaftor 152-162 CF transmembrane conductance regulator Homo sapiens 67-71 29327948-1 2018 RATIONALE: The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. lumacaftor 103-113 CF transmembrane conductance regulator Homo sapiens 34-38 29327948-1 2018 RATIONALE: The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. lumacaftor 103-113 CF transmembrane conductance regulator Homo sapiens 40-91 29327948-3 2018 OBJECTIVES: To examine the effect of lumacaftor-ivacaftor on biomarkers of CFTR function in Phe508del homozygous patients with cystic fibrosis aged 12 years and older. lumacaftor 37-47 CF transmembrane conductance regulator Homo sapiens 75-79 29327948-8 2018 CONCLUSIONS: Lumacaftor-ivacaftor results in partial rescue of Phe508del CFTR function to levels comparable to the lower range of CFTR activity found in patients with residual function mutations. lumacaftor 13-23 CF transmembrane conductance regulator Homo sapiens 73-77 29914743-1 2018 Lumacaftor/ivacaftor is a precision medicine targeting the defective cystic fibrosis transmembrane regulator (CFTR) protein in cystic fibrosis (CF) patients homozygous for Phe508del genotype. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 69-108 29538046-6 2018 A next-generation CFTR corrector, tezacaftor, with ivacaftor equally effective and better tolerated than lumacaftor, has also received US Food and Drug Administration approval. lumacaftor 105-115 CF transmembrane conductance regulator Homo sapiens 18-22 29572333-8 2018 Only idelalisib showed strong inhibition of CYP3A, and lumacaftor behaved as a strong CYP3A inducer. lumacaftor 55-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-91 29914743-1 2018 Lumacaftor/ivacaftor is a precision medicine targeting the defective cystic fibrosis transmembrane regulator (CFTR) protein in cystic fibrosis (CF) patients homozygous for Phe508del genotype. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 110-114 29202459-7 2017 However, nasospheroids from F508del CF homozygotes that were treated with lumacaftor and ivacaftor showed a significant reduction in cross-sectional area, indicating pharmacologic rescue of CFTR function. lumacaftor 74-84 CF transmembrane conductance regulator Homo sapiens 190-194 29461009-2 2018 Lumacaftor/Ivacaftor is a novel CFTR modulator approved for patients that are homozygous for Phe508del CFTR, but its clinical effectiveness varies amongst patients, making it difficult to determine clinical responders. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 32-36 29020304-10 2018 Lumacaftor significantly shortened cFPD in Class 2 iPSC-CMs by correcting the hERG trafficking defect. lumacaftor 0-10 ETS transcription factor ERG Homo sapiens 78-82 29384380-1 2018 The most promising F508del-CFTR corrector, VX-809, has been unsuccessful as an effective, stand-alone treatment for CF patients, but the rescue effect in combination with other drugs may confer an acceptable level of therapeutic benefit. lumacaftor 43-49 CF transmembrane conductance regulator Homo sapiens 27-31 29451946-2 2018 The combination of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been shown to increase forced expiratory volume in 1 second (FEV1) moderately, but predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic fibrosis patients; however, patients with FEV1 <40% predicted were excluded from studies. lumacaftor 92-102 CF transmembrane conductance regulator Homo sapiens 23-74 29451946-2 2018 The combination of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been shown to increase forced expiratory volume in 1 second (FEV1) moderately, but predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic fibrosis patients; however, patients with FEV1 <40% predicted were excluded from studies. lumacaftor 92-102 CF transmembrane conductance regulator Homo sapiens 76-80 28978522-7 2018 F508del-CFTR channels that had been rescued by the CF drug combination VX-809 (lumacaftor) + VX-770 (ivacaftor) were more sensitive to this downregulation than wild-type CFTR. lumacaftor 79-89 CF transmembrane conductance regulator Homo sapiens 8-12 29351449-7 2018 In recent years, two modulators, ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S. Food and Drug Administration to treat CF patients with certain CFTR mutations. lumacaftor 58-68 CF transmembrane conductance regulator Homo sapiens 184-188 29318594-5 2018 By contrast, CFFT-004 rescued F508del-CFTR channel gating better than C18, an analogue of the clinically used CFTR corrector lumacaftor. lumacaftor 125-135 CF transmembrane conductance regulator Homo sapiens 110-114 29232160-6 2018 In CF cells, lumacaftor (3 muM) and ivacaftor (10 muM) corrected mutant F508del CFTR. lumacaftor 13-23 CF transmembrane conductance regulator Homo sapiens 80-84 29232160-9 2018 Exogenous TGF-beta doubles miR-145 expression (P < 0.05), halves wild-type CFTR mRNA and protein levels (P < 0.01), and nullifies lumacaftor/ivacaftor F508del CFTR correction. lumacaftor 136-146 transforming growth factor beta 1 Homo sapiens 10-18 29232160-11 2018 miR-145 antagonism blocks TGF-beta suppression of CFTR and enhances lumacaftor correction of F508del CFTR. lumacaftor 68-78 microRNA 145 Homo sapiens 0-7 29232160-11 2018 miR-145 antagonism blocks TGF-beta suppression of CFTR and enhances lumacaftor correction of F508del CFTR. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 101-105 29126871-0 2018 Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 103-107 29126871-2 2018 METHODS: Patients with CF 12 years of age and older, homozygous for F508del-CFTR, with percent predicted forced expiratory volume in 1 second (ppFEV1) <40 received lumacaftor 400 mg/ivacaftor 250mg every 12h (full dose) for 24weeks in an open-label, prospective study (NCT02390219). lumacaftor 164-174 CF transmembrane conductance regulator Homo sapiens 76-80 29497617-9 2018 Nonfunctional channels were subjected to CFTR-directed ivacaftor-lumacaftor treatments. lumacaftor 65-75 CF transmembrane conductance regulator Homo sapiens 41-45 29426890-13 2018 We highlight the elevated expression level of GMPR in AD and propose a therapeutic strategy of inhibiting GMPR1 with lumacaftor. lumacaftor 117-127 guanosine monophosphate reductase Mus musculus 46-50 29426890-13 2018 We highlight the elevated expression level of GMPR in AD and propose a therapeutic strategy of inhibiting GMPR1 with lumacaftor. lumacaftor 117-127 guanosine monophosphate reductase Mus musculus 106-111 28846049-1 2017 INTRODUCTION: Lumacaftor-ivacaftor is indicated for treatment of cystic fibrosis (CF) in patients homozygous for the Phe-508del cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. lumacaftor 14-24 CF transmembrane conductance regulator Homo sapiens 128-179 28846049-1 2017 INTRODUCTION: Lumacaftor-ivacaftor is indicated for treatment of cystic fibrosis (CF) in patients homozygous for the Phe-508del cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. lumacaftor 14-24 CF transmembrane conductance regulator Homo sapiens 181-185 28846049-8 2017 Lumacaftor is a strong inducer of CYP3A while ivacaftor is a CYP3A sensitive substrate. lumacaftor 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-39 29155707-2 2017 Ivacaftor (IVA) and ivacaftor-lumacaftor (LUMA) combination are two new breakthrough CF drugs that directly modulate the activity and trafficking of the defective CFTR-protein. lumacaftor 30-40 CF transmembrane conductance regulator Homo sapiens 163-167 28529073-1 2017 The combination of lumacaftor and ivacaftor (LUM/IVA) has been reported to induce a mean acute absolute drop of -4.1% predicted forced expiratory volume in 1s (FEV1) after a unique administration in healthy subjects. lumacaftor 19-29 lumican Homo sapiens 45-48 28366727-0 2017 Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR. lumacaftor 10-16 CF transmembrane conductance regulator Homo sapiens 111-115 28785019-8 2017 The CFTR correctors lumacaftor and tezacaftor significantly increased the IscF/I+V response to about 25% (SEM = 4.4) of the WT-CFTR level and the CFTR apical expression to about 22% (SEM = 4.6) of the WT-CFTR level in F508del/F508del HNE cells. lumacaftor 20-30 CF transmembrane conductance regulator Homo sapiens 4-8 28785019-8 2017 The CFTR correctors lumacaftor and tezacaftor significantly increased the IscF/I+V response to about 25% (SEM = 4.4) of the WT-CFTR level and the CFTR apical expression to about 22% (SEM = 4.6) of the WT-CFTR level in F508del/F508del HNE cells. lumacaftor 20-30 CF transmembrane conductance regulator Homo sapiens 128-132 28785019-8 2017 The CFTR correctors lumacaftor and tezacaftor significantly increased the IscF/I+V response to about 25% (SEM = 4.4) of the WT-CFTR level and the CFTR apical expression to about 22% (SEM = 4.6) of the WT-CFTR level in F508del/F508del HNE cells. lumacaftor 20-30 CF transmembrane conductance regulator Homo sapiens 128-132 28785019-8 2017 The CFTR correctors lumacaftor and tezacaftor significantly increased the IscF/I+V response to about 25% (SEM = 4.4) of the WT-CFTR level and the CFTR apical expression to about 22% (SEM = 4.6) of the WT-CFTR level in F508del/F508del HNE cells. lumacaftor 20-30 CF transmembrane conductance regulator Homo sapiens 128-132 28769592-4 2017 In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. lumacaftor 68-78 CF transmembrane conductance regulator Homo sapiens 163-214 28366727-5 2017 To investigate whether VX-809 promoted CL1/NBD1 interactions, we performed cysteine mutagenesis and disulfide cross-linking analysis of Cys-less TMD1 (residues 1-436) and DeltaTMD1 (residues 437-1480; NBD1-R-TMD2-NBD2) truncation mutants. lumacaftor 23-29 adhesion G protein-coupled receptor L1 Homo sapiens 39-42 28366727-7 2017 Expression in the presence of VX-809 also promoted cross-linking between R170C (in CL1 of TMD1 protein) and L475C (in NBD1 of the DeltaTMD1 truncation protein). lumacaftor 30-36 adhesion G protein-coupled receptor L1 Homo sapiens 83-86 28366727-9 2017 The results suggest that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. lumacaftor 48-54 CF transmembrane conductance regulator Homo sapiens 92-96 28366727-9 2017 The results suggest that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. lumacaftor 48-54 adhesion G protein-coupled receptor L1 Homo sapiens 113-116 29032041-4 2017 Modest enhancement of F508del-CFTR function has been achieved by combining Ivacaftor with Lumacaftor, a compound that aids maturational processing of misfolded CFTR. lumacaftor 90-100 CF transmembrane conductance regulator Homo sapiens 30-34 28606620-1 2017 BACKGROUND: Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 146-205 28606620-1 2017 BACKGROUND: Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 207-211 28606620-1 2017 BACKGROUND: Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 316-320 28606620-2 2017 We report efficacy and safety of lumacaftor and ivacaftor in patients with cystic fibrosis aged 6-11 years homozygous for F508del-CFTR. lumacaftor 33-43 CF transmembrane conductance regulator Homo sapiens 130-134 28606620-22 2017 INTERPRETATION: Treatment with lumacaftor and ivacaftor was associated with statistically significant improvements in lung function, as measured by LCI2 5 and ppFEV1, versus placebo in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR. lumacaftor 31-41 CF transmembrane conductance regulator Homo sapiens 254-258 29032041-4 2017 Modest enhancement of F508del-CFTR function has been achieved by combining Ivacaftor with Lumacaftor, a compound that aids maturational processing of misfolded CFTR. lumacaftor 90-100 CF transmembrane conductance regulator Homo sapiens 160-164 27805836-0 2017 Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 97-101 27983869-9 2017 There were differences in cell morphology and current magnitude as a function of extended passage, but the effect of VX-809 in increasing CFTR function was significant in CRC-expanded F508 del HBE cells. lumacaftor 117-123 CF transmembrane conductance regulator Homo sapiens 138-142 27805836-1 2017 RATIONALE: Combination lumacaftor/ivacaftor has been shown to improve lung function and other endpoints in patients aged 12 years and older with cystic fibrosis and homozygous for F508del-CFTR, but it has not been assessed in younger patients. lumacaftor 23-33 CF transmembrane conductance regulator Homo sapiens 188-192 28362199-0 2017 Effects of Lumacaftor/Ivacaftor in a Pediatric Cohort Homozygous for F508del-CFTR. lumacaftor 11-21 CF transmembrane conductance regulator Homo sapiens 77-81 27898234-0 2017 Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 89-93 28087700-7 2017 Lumacaftor partially stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl- channels. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 61-65 28087700-7 2017 Lumacaftor partially stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl- channels. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 122-126 28087700-9 2017 Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl- currents. lumacaftor 72-82 CF transmembrane conductance regulator Homo sapiens 45-49 28087700-9 2017 Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl- currents. lumacaftor 72-82 CF transmembrane conductance regulator Homo sapiens 129-133 28087700-11 2017 We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl- channels but that the majority remain destabilized. lumacaftor 25-35 CF transmembrane conductance regulator Homo sapiens 118-122 28087700-2 2017 Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. lumacaftor 40-50 CF transmembrane conductance regulator Homo sapiens 25-29 27898234-1 2017 RATIONALE: In a prior study, lumacaftor/ivacaftor treatment (<=28 d) in patients with cystic fibrosis (CF) heterozygous for F508del-CFTR did not improve lung function. lumacaftor 29-39 CF transmembrane conductance regulator Homo sapiens 135-139 27898234-2 2017 OBJECTIVES: To evaluate an optimized lumacaftor/ivacaftor dosing regimen with a longer duration in a cohort of patients heterozygous for F508del-CFTR. lumacaftor 37-47 CF transmembrane conductance regulator Homo sapiens 145-149 28011037-1 2017 BACKGROUND: The 24-week safety and efficacy of lumacaftor/ivacaftor combination therapy was shown in two randomised controlled trials (RCTs)-TRAFFIC and TRANSPORT-in patients with cystic fibrosis who were aged 12 years or older and homozygous for the F508del-CFTR mutation. lumacaftor 47-57 CF transmembrane conductance regulator Homo sapiens 259-263 27895116-5 2017 Corrector scaffolds of 1-arylpyrazole-4-arylsulfonyl-piperazine and spiro-piperidine-quinazolinone classes were identified with up to ~5-fold greater efficacy than VX-809, some of which were selective for CFTR1281, whereas others also corrected DeltaF508-CFTR. lumacaftor 164-170 CF transmembrane conductance regulator Homo sapiens 205-209 28001373-7 2017 The combination of VX-809 with either low temperature or the I539T mutation increased the amount of CFTR on the plasma membrane to nearly 40%, indicating synergistic activity. lumacaftor 19-25 CF transmembrane conductance regulator Homo sapiens 100-104 27804127-2 2017 The recent US Food and Drug Administration (FDA) approval of lumacaftor combined with ivacaftor (Orkambi) targets patients with the F508del-CFTR. lumacaftor 61-71 CF transmembrane conductance regulator Homo sapiens 140-144 27660821-5 2016 We also demonstrate that emerging CF treatments - ivacaftor and lumacaftor - can mediate pronounced pharmacologic activation of P67L CFTR. lumacaftor 64-74 CF transmembrane conductance regulator Homo sapiens 133-137 27821435-7 2017 The most significant changes for inhibition and induction were observed with rolapitant, a moderate inhibitor of CYP2D6 and lumacaftor, a strong inducer of CYP3A. lumacaftor 124-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-161 26806675-6 2016 In phe508del homozygous patients, the combination of ivacaftor with a CFTR corrector (lumacaftor) has also led to respiratory improvement, albeit less impressive. lumacaftor 86-96 CF transmembrane conductance regulator Homo sapiens 70-74 27394157-1 2016 Lumacaftor/ivacaftor (Orkambi ) is a fixed-dose tablet containing a corrector (lumacaftor) and potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (aged >=12 years) homozygous for the most common CFTR mutation, F508del. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 126-177 27402691-8 2016 We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. lumacaftor 14-20 CF transmembrane conductance regulator Homo sapiens 37-41 27394157-1 2016 Lumacaftor/ivacaftor (Orkambi ) is a fixed-dose tablet containing a corrector (lumacaftor) and potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (aged >=12 years) homozygous for the most common CFTR mutation, F508del. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 179-183 27394157-1 2016 Lumacaftor/ivacaftor (Orkambi ) is a fixed-dose tablet containing a corrector (lumacaftor) and potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (aged >=12 years) homozygous for the most common CFTR mutation, F508del. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 332-336 27394157-2 2016 Lumacaftor improves the processing of F508del CFTR and its transport to the cell surface, while ivacaftor increases the channel"s open probability and transport of chloride. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 46-50 27394157-7 2016 Thus, lumacaftor/ivacaftor expands the treatment options available for patients with cystic fibrosis homozygous for the F508del-CFTR mutation, although its precise place in clinical practice remains to be determined. lumacaftor 6-16 CF transmembrane conductance regulator Homo sapiens 128-132 27298017-0 2016 Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis. lumacaftor 23-33 CF transmembrane conductance regulator Homo sapiens 122-126 27298017-18 2016 INTERPRETATION: These analyses confirm that lumacaftor/ivacaftor combination therapy benefits patients with cystic fibrosis homozygous for Phe508del CFTR who have varying degrees of lung function impairment. lumacaftor 44-54 CF transmembrane conductance regulator Homo sapiens 149-153 27168400-6 2016 Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor) restored the mutant function to ~50% of the wild-type channel in primary CFTRDeltaF508/DeltaF508 human bronchial epithelia. lumacaftor 56-62 ribosomal protein L12 Homo sapiens 15-20 27168400-6 2016 Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor) restored the mutant function to ~50% of the wild-type channel in primary CFTRDeltaF508/DeltaF508 human bronchial epithelia. lumacaftor 64-74 ribosomal protein L12 Homo sapiens 15-20 27252987-5 2016 This article reviews the rationale, progress and future direction in the development of lumacaftor/ivacaftor combination to treat CF patients homozygous for the Phe508del-CFTR mutation. lumacaftor 88-98 CF transmembrane conductance regulator Homo sapiens 171-175 26677762-2 2016 We aimed to demonstrate that the resulting altered properties of mucus can be recovered using lumacaftor, a CFTR corrector. lumacaftor 94-104 CF transmembrane conductance regulator Homo sapiens 108-112 26677762-5 2016 We found that 25% correction of F508del-CFTR mutation with lumacaftor was enough to improve significantly CF mucus properties. lumacaftor 59-69 CF transmembrane conductance regulator Homo sapiens 40-44 26823603-4 2016 Both the small molecules trimethylangelicin (TMA) and VX-809, which act as "correctors" for F508del CFTR by rescuing F508del-CFTR-dependent chloride secretion, also restore the apical expression of phosphorylated ezrin and actin organization and increase cAMP and activated PKA submembrane compartmentalization in both primary and secondary cystic fibrosis airway cells. lumacaftor 54-60 CF transmembrane conductance regulator Homo sapiens 100-104 26823603-5 2016 Latrunculin B treatment or expression of the inactive ezrin mutant T567A reverse the TMA and VX-809-induced effects highlighting the role of corrector-dependent ezrin activation and actin re-organization in creating the conditions to generate a sub-cortical cAMP pool of adequate amplitude to activate the F508del-CFTR-dependent chloride secretion. lumacaftor 93-99 CF transmembrane conductance regulator Homo sapiens 314-318 27252987-0 2016 Lumacaftor/ivacaftor combination for cystic fibrosis patients homozygous for Phe508del-CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 87-91 26823603-4 2016 Both the small molecules trimethylangelicin (TMA) and VX-809, which act as "correctors" for F508del CFTR by rescuing F508del-CFTR-dependent chloride secretion, also restore the apical expression of phosphorylated ezrin and actin organization and increase cAMP and activated PKA submembrane compartmentalization in both primary and secondary cystic fibrosis airway cells. lumacaftor 54-60 CF transmembrane conductance regulator Homo sapiens 125-129 26863533-8 2016 Combination treatment with CP7q and VX-809, a corrector of DeltaF508-CFTR, significantly enhanced functional rescue of DeltaF508-CFTR compared with VX-809 alone. lumacaftor 36-42 CF transmembrane conductance regulator Homo sapiens 69-73 26863533-8 2016 Combination treatment with CP7q and VX-809, a corrector of DeltaF508-CFTR, significantly enhanced functional rescue of DeltaF508-CFTR compared with VX-809 alone. lumacaftor 36-42 CF transmembrane conductance regulator Homo sapiens 129-133 26863533-8 2016 Combination treatment with CP7q and VX-809, a corrector of DeltaF508-CFTR, significantly enhanced functional rescue of DeltaF508-CFTR compared with VX-809 alone. lumacaftor 148-154 CF transmembrane conductance regulator Homo sapiens 129-133 26581802-5 2016 We summarize experience with lumacaftor, a small molecule that increases F508del-CFTR levels at the plasma membrane. lumacaftor 29-39 CF transmembrane conductance regulator Homo sapiens 81-85 26506855-0 2016 Response to: "Lumacaftor/ivacaftor for patients homozygous for Phe508del-CFTR: should we curb our enthusiasm?" lumacaftor 14-24 CF transmembrane conductance regulator Homo sapiens 73-77 26336913-7 2016 Treatment of cells with the C4+VX-809 combination resulted in enhanced rescue and 2-fold higher forskolin+IBMX-activated currents of both I507-ATT and I507-ATC DeltaF508 CFTR, compared with VX-809 treatment alone. lumacaftor 31-37 CF transmembrane conductance regulator Homo sapiens 170-174 26581802-6 2016 Lumacaftor in combination with ivacaftor, a modulator of CFTR gating defects, improves clinical outcome measures in patients homozygous for the F508del mutation. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 57-61 26336913-7 2016 Treatment of cells with the C4+VX-809 combination resulted in enhanced rescue and 2-fold higher forskolin+IBMX-activated currents of both I507-ATT and I507-ATC DeltaF508 CFTR, compared with VX-809 treatment alone. lumacaftor 190-196 complement C4A (Rodgers blood group) Homo sapiens 28-30 27482545-0 2016 Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation. lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 106-110 26183966-5 2015 Our analysis identified RNF5 as a protein whose inhibition promoted significant F508del-CFTR rescue and displayed an additive effect with the investigational drug VX-809. lumacaftor 163-169 ring finger protein 5 Homo sapiens 24-28 27482545-4 2016 The corrector lumacaftor helps rescue F508del-CFTR to the cell surface, and potentiator ivacaftor increases F508del-CFTR channel activity. lumacaftor 14-24 CF transmembrane conductance regulator Homo sapiens 46-50 26510034-0 2015 Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 79-83 26510035-0 2015 Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 79-83 26227551-3 2015 VX-809 has been reported to facilitate the folding and trafficking of F508del-CFTR and augment its channel function. lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 78-82 26227551-7 2015 By using Cu(I) -catalyzed click chemistry, we provide evidence that the VX-809 derivatives bind CFTR directly in vitro and in cells. lumacaftor 72-78 CF transmembrane conductance regulator Homo sapiens 96-100 26171232-0 2015 Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR. lumacaftor 22-28 cystic fibrosis transmembrane conductance regulator Mesocricetus auratus 113-117 26171232-3 2015 Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. lumacaftor 61-67 cystic fibrosis transmembrane conductance regulator Mesocricetus auratus 21-25 26171232-3 2015 Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. lumacaftor 61-67 cystic fibrosis transmembrane conductance regulator Mesocricetus auratus 92-96 26171232-9 2015 Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. lumacaftor 41-47 cystic fibrosis transmembrane conductance regulator Mesocricetus auratus 81-85 26171232-11 2015 Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue. lumacaftor 22-28 cystic fibrosis transmembrane conductance regulator Mesocricetus auratus 64-68 24726831-0 2014 VX-809 and related corrector compounds exhibit secondary activity stabilizing active F508del-CFTR after its partial rescue to the cell surface. lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 93-97 26071414-0 2015 Lumacaftor/ivacaftor for patients homozygous for Phe508del-CFTR: should we curb our enthusiasm? lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 59-63 26018799-0 2015 Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells. lumacaftor 31-37 CF transmembrane conductance regulator Homo sapiens 57-61 26018799-3 2015 Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. lumacaftor 37-43 CF transmembrane conductance regulator Homo sapiens 79-83 26018799-3 2015 Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. lumacaftor 37-43 CF transmembrane conductance regulator Homo sapiens 293-297 26018799-6 2015 The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. lumacaftor 14-20 CF transmembrane conductance regulator Homo sapiens 32-36 25990958-6 2015 Because binding of F508del-CFTR to the second PDZ of NHERF1 precluded the recruitment of CHIP, the coexposure of airway cells to Rac1 activator nearly tripled the efficacy of VX-809. lumacaftor 175-181 CF transmembrane conductance regulator Homo sapiens 27-31 25990958-6 2015 Because binding of F508del-CFTR to the second PDZ of NHERF1 precluded the recruitment of CHIP, the coexposure of airway cells to Rac1 activator nearly tripled the efficacy of VX-809. lumacaftor 175-181 SLC9A3 regulator 1 Homo sapiens 53-59 25990958-6 2015 Because binding of F508del-CFTR to the second PDZ of NHERF1 precluded the recruitment of CHIP, the coexposure of airway cells to Rac1 activator nearly tripled the efficacy of VX-809. lumacaftor 175-181 Rac family small GTPase 1 Homo sapiens 129-133 25971311-6 2015 EXPERT OPINION: Cyclopropane carboxamide derivatives of CFTR correctors continue to dominate in this area, among which lumacaftor (a NBD1-MSD1/2 interface stabilizer) is the most promising compound and is now under the priority review by US FDA. lumacaftor 119-129 CF transmembrane conductance regulator Homo sapiens 56-60 25981758-0 2015 Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 79-83 24796242-0 2014 Combined effects of VX-770 and VX-809 on several functional abnormalities of F508del-CFTR channels. lumacaftor 31-37 CF transmembrane conductance regulator Homo sapiens 85-89 24737137-0 2014 Synergy-based small-molecule screen using a human lung epithelial cell line yields DeltaF508-CFTR correctors that augment VX-809 maximal efficacy. lumacaftor 122-128 CF transmembrane conductance regulator Homo sapiens 93-97 24095197-6 2014 Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 25-29 24095197-6 2014 Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. lumacaftor 12-18 CF transmembrane conductance regulator Homo sapiens 25-29 23924900-9 2013 These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR. lumacaftor 35-41 CF transmembrane conductance regulator Homo sapiens 162-166 23924900-9 2013 These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR. lumacaftor 35-41 CF transmembrane conductance regulator Homo sapiens 162-166 23890012-2 2013 VX-809 is a small molecule that rescues F508del-CFTR localization, which recently went into clinical trial but with unknown mechanism of action (MoA). lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 48-52 22739718-15 2012 CONCLUSIONS: Three new agents, ivacaftor, VX-809, and ataluren, target the basic defects in CFTR production. lumacaftor 42-48 CF transmembrane conductance regulator Homo sapiens 92-96 23666117-2 2013 VX-809, a promising investigational corrector of DeltaF508-CFTR misprocessing, has limited clinical benefit and an incompletely understood mechanism, hampering drug development. lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 59-63 33808590-2 2021 Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. lumacaftor 57-67 CF transmembrane conductance regulator Homo sapiens 29-33 33808590-0 2021 CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis. lumacaftor 28-38 CF transmembrane conductance regulator Homo sapiens 0-4 21976485-4 2011 Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. lumacaftor 46-52 CF transmembrane conductance regulator Homo sapiens 56-60 21976485-5 2011 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. lumacaftor 100-106 CF transmembrane conductance regulator Homo sapiens 124-128 21976485-5 2011 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. lumacaftor 100-106 CF transmembrane conductance regulator Homo sapiens 353-357 21976485-7 2011 VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 46-50 21976485-8 2011 VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR. lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 29-33 21976485-8 2011 VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR. lumacaftor 0-6 CF transmembrane conductance regulator Homo sapiens 116-120 34662459-6 2021 Our co-localization studies confirmed that cystic fibrosis transmembrane conductance regulator (CFTR) is found predominately at the apical membrane in the untreated animals of each age group, consistent with its role in Cl- secretion; after VX-809 treatment, the basolateral membrane co-localization of CFTR increased ~4-fold, accompanied by a decrease of ~2-3-fold in its apical co-localization, indicating that VX-809 alters the phenotype to favor fluid absorption. lumacaftor 241-247 cystic fibrosis transmembrane conductance regulator Mus musculus 303-307 33805605-8 2021 We now have evidence that Matrine and Lumacaftor not only restore the transport of mutant CFTR protein, but probably also counteract the inflammatory process by improving the course of the disease. lumacaftor 38-48 CF transmembrane conductance regulator Homo sapiens 90-94 34905942-11 2022 Pharmacologically stabilizing CFTR expression in vivo (3 mg/kg lumacaftor for 2 days) eliminates the rhythmicity in myogenic reactivity and abolishes the circadian variation in SAH-induced neurological injury. lumacaftor 63-73 cystic fibrosis transmembrane conductance regulator Mus musculus 30-34 34795038-1 2021 OBJECTIVES: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 38-89 34795038-1 2021 OBJECTIVES: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). lumacaftor 12-22 CF transmembrane conductance regulator Homo sapiens 91-95 34869102-1 2021 Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. lumacaftor 50-60 CF transmembrane conductance regulator Homo sapiens 35-39 34869102-1 2021 Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. lumacaftor 62-65 CF transmembrane conductance regulator Homo sapiens 35-39 34793977-4 2022 These drugs, called CFTR modulators, have been advanced to the clinics to treat nearly 90% of CF patients, including the CFTR potentiator ivacaftor, approved for residual function mutations (Classes III and IV), and combinations of correctors (lumacaftor, tezacaftor, elexacaftor) and ivacaftor for patients bearing at least one the F508del mutation, the most frequent mutation belonging to class II. lumacaftor 244-254 CF transmembrane conductance regulator Homo sapiens 20-24 34662459-6 2021 Our co-localization studies confirmed that cystic fibrosis transmembrane conductance regulator (CFTR) is found predominately at the apical membrane in the untreated animals of each age group, consistent with its role in Cl- secretion; after VX-809 treatment, the basolateral membrane co-localization of CFTR increased ~4-fold, accompanied by a decrease of ~2-3-fold in its apical co-localization, indicating that VX-809 alters the phenotype to favor fluid absorption. lumacaftor 413-419 cystic fibrosis transmembrane conductance regulator Mus musculus 43-94 34662459-6 2021 Our co-localization studies confirmed that cystic fibrosis transmembrane conductance regulator (CFTR) is found predominately at the apical membrane in the untreated animals of each age group, consistent with its role in Cl- secretion; after VX-809 treatment, the basolateral membrane co-localization of CFTR increased ~4-fold, accompanied by a decrease of ~2-3-fold in its apical co-localization, indicating that VX-809 alters the phenotype to favor fluid absorption. lumacaftor 413-419 cystic fibrosis transmembrane conductance regulator Mus musculus 96-100 34662459-6 2021 Our co-localization studies confirmed that cystic fibrosis transmembrane conductance regulator (CFTR) is found predominately at the apical membrane in the untreated animals of each age group, consistent with its role in Cl- secretion; after VX-809 treatment, the basolateral membrane co-localization of CFTR increased ~4-fold, accompanied by a decrease of ~2-3-fold in its apical co-localization, indicating that VX-809 alters the phenotype to favor fluid absorption. lumacaftor 413-419 cystic fibrosis transmembrane conductance regulator Mus musculus 303-307 34083123-2 2022 Lumacaftor-ivacaftor is approved for use in people with cystic fibrosis (CF) carrying two copies of F508del-CFTR. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 108-112 34454846-8 2022 Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. lumacaftor 165-175 glutamic--pyruvic transaminase Homo sapiens 16-40 34454846-8 2022 Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. lumacaftor 165-175 solute carrier family 17 member 5 Homo sapiens 48-74 34454846-8 2022 Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. lumacaftor 165-175 solute carrier family 17 member 5 Homo sapiens 76-79 35282377-0 2022 What Is the Potential for Lumacaftor as a Chemical Chaperone in Promoting hERG Trafficking? lumacaftor 26-36 ETS transcription factor ERG Homo sapiens 74-78 34329764-12 2021 Whereas, treatment with VX-809, increasing Hsp27 or inhibiting HSP70 or 90 restored CFTR localization toward normal values. lumacaftor 24-30 heat shock protein family A (Hsp70) member 4 Homo sapiens 63-68 34329764-12 2021 Whereas, treatment with VX-809, increasing Hsp27 or inhibiting HSP70 or 90 restored CFTR localization toward normal values. lumacaftor 24-30 CF transmembrane conductance regulator Homo sapiens 84-88 35210618-5 2022 We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized DeltaF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. lumacaftor 74-84 OTU deubiquitinase, ubiquitin aldehyde binding 1 Homo sapiens 48-53 35210618-5 2022 We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized DeltaF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. lumacaftor 74-84 CF transmembrane conductance regulator Homo sapiens 143-195 35210618-5 2022 We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized DeltaF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. lumacaftor 74-84 CF transmembrane conductance regulator Homo sapiens 197-201 35210618-5 2022 We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized DeltaF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. lumacaftor 74-84 CF transmembrane conductance regulator Homo sapiens 234-238 34995514-4 2022 To investigate the molecular mechanism of their action, we determined cryo-electron microscopy structures of CFTR in complex with the FDA-approved correctors lumacaftor or tezacaftor. lumacaftor 158-168 CF transmembrane conductance regulator Homo sapiens 109-113 35207740-1 2022 Lumacaftor/ivacaftor (LUMA-IVA) therapy is prescribed to people with cystic fibrosis (pwCF) homozygous for the Phe508del-CFTR variant to restore CFTR protein function. lumacaftor 0-10 transmembrane protein 43 Homo sapiens 22-26 35207740-1 2022 Lumacaftor/ivacaftor (LUMA-IVA) therapy is prescribed to people with cystic fibrosis (pwCF) homozygous for the Phe508del-CFTR variant to restore CFTR protein function. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 121-125 35207740-1 2022 Lumacaftor/ivacaftor (LUMA-IVA) therapy is prescribed to people with cystic fibrosis (pwCF) homozygous for the Phe508del-CFTR variant to restore CFTR protein function. lumacaftor 0-10 CF transmembrane conductance regulator Homo sapiens 145-149