Fig. 7. CFTR function is restored by SRI-37240 and SRI-41315 in combination with G418 in primary bronchial epithelial cells derived from a CF patient with CFTR nonsense alleles.
Primary HBE cells derived from a donor with an R553X/W1282X CFTR genotype were grown at an air–liquid interface until terminally differentiated and then treated with SRI-37240 (10 µM) or SRI-41315 (5 µM) alone or in combination with G418 (100 µM) for 72 h and then CFTR function was the measured. a Representative Ieq traces after acute treatments with benzamil (10 µM), forskolin (10 µM) + ivacaftor (1 µM), and bumetanide (20 µM). b Corresponding average current calculated from the area under the curve between forskolin/ivacaftor-induced CFTR activity onset and anion transport inhibition with bumetanide (n = 3, data are expressed as mean ± S.D. and statistically analyzed using ordinary one-way ANOVA followed by Tukey’s post hoc test, **p = 0.0010 (G418 vs SRI-41315 + G418), ***p = 0.0001 (SRI-41315 vs SRI-41315 + G418), ****p < 0.0001 (Vehicle vs SRI-41315 + G418). c Transepithelial electrical resistance (TEER) values for the treatment conditions in panels (a) and (b) prior to electrophysiologic agonists (n = 3, data are expressed as mean ± S.D. and statistically analyzed using ordinary one-way ANOVA (P = NS)); for all panels, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. Source data is available as a source data file.