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. 2021 May 17;22(10):5262. doi: 10.3390/ijms22105262

Figure 2.

Figure 2

Functional evaluation of VX-445 corrector activity in human bronchial epithelial cells. (A) Effect of 24 h cell treatment with vehicle alone (DMSO), VX-445 (5 µM), VX-809 (1 µM), or both correctors together. Experiments were done on F508del/F508del bronchial epithelial cells derived from 5 different subjects (BE86, BE91, BE93, BE111, and BE115) with the short-circuit current technique. Representative recordings are from BE115. As parameters of CFTR function, we measured the total current sensitive to inh-172 (ITOT) and the current elicited by the cAMP analog alone (IcAMP). (B) Representative trace obtained from short-circuit current recordings on non-CF bronchial epithelial cells (BE99). (C) Summary of ITOT (mean ± SD, n = 26–31) measured in F508del/F508del epithelia, derived from 5 different subjects (BE86, BE91, BE93, BE111, and BE115), exposed to indicated treatments. The dashed line reports the value of ITOT in non-CF bronchial cells. *, p < 0.05; ***, p < 0.001 between indicated groups of data. (D) Ratio between the current elicited by cAMP stimulation (IcAMP) and total CFTR current (ITOT) in F508del/F508del epithelia treated with the indicated compounds (data obtained from experiments shown in A and C). *, p < 0.05; ***, p < 0.001 between indicated groups of data. (E) Evaluation of VX-445 as potentiator on F508del-CFTR CFBE41o- cells rescued at 32 °C for 24 h (mean ± SD, n = 5). ***, p < 0.001 vs. control.