Cystic fibrosis is caused by a reduced quantity or function of cystic fibrosis transmembrane conductance regulator (CFTR) protein, owing to mutations in CFTR. VX-661 is a first-generation CFTR corrector that has shown enhanced CFTR function and improved lung function in a phase 2 clinical trial involving patients who were homozygous for the Phe508del mutation or heterozygous for the Phe508del and G551D mutations [3]. The combination of VX-445 (2 μM) and VX-661 (18 μM) increased levels of mature CFTR protein and led to an increase in human bronchial epithelial cells from Phe508del–MF (a minimal-function mutation) and Phe508del–Phe508del (the Phe508del CFTR mutation) donors [4]. All doses of [VX-659-VX-661-ivacaftor] resulted in significant improvement in the percentage of predicted FEV1 (forced expiratory volume in 1 second) as compared with the respective within-group baseline values at day 29 in patients with Phe508del-MF or Phe508del-Phe508del genotypes [5].
Tezacaftor 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CF monocytes
5 µM
24 h
To evaluate the effect of Tezacaftor in combination with Ivacaftor on IL-18 and IL-1β levels in CF monocytes. Results showed that IVA/TEZ significantly reduced the secretion of IL-18 and IL-1β after LPS/ATP stimulation.
Elife. 2020 Mar 2;9:e54556.
CFBE41o-(F508del)
3 μM
72 h
To evaluate the effect of Tezacaftor in combination with Triple therapy on CFTR protein levels in CFBE41o-(F508del) cells, results showed that the combination of Tezacaftor with Triple therapy significantly increased total CFTR protein levels.
Front Pharmacol. 2022 May 20;13:876842.
Tezacaftor 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
F508del/F508del mouse model
Oral
21 mg/kg
Once daily for 14 days
To evaluate the effect of Tezacaftor in combination with Triple therapy on lung function in F508del/F508del mice, results showed that the combination of Tezacaftor with Triple therapy significantly improved lung function.
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