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. 2023 Jan 30;9(1):00495-2022. doi: 10.1183/23120541.00495-2022

FIGURE 4.

FIGURE 4

Statins increase forskolin-induced swelling (FIS) in homozygous W1282X/W1282X patient-derived intestinal organoids (PDIOs) in a concentration-dependent manner. a) Area under the curve (AUC) values of the secondary FIS screen for two W1282X/W1282X PDIOs, in which compounds of the primary screen top five were tested separately and as original combination. Trikafta (CFTR modulators VX-445/VX-661/VX-770) was used as background. b) AUC values for two W1282X/W1282X PDIOs upon treatment with the statins and CFTR modulators separately (all at 3 µM), as well as the combination and a positive control consisting of 80 µM ELX-02, 0.3 µM SMG1i and 3 µM VX-445/VX-661/VX-770 (Trikafta). Means are shown of three biological replicate experiments with three technical replicates per condition; sem is indicated by error bars. c) Curve-fitting line for AUC values of W1282X/W1282X PDIO line 1 upon a mevastatin and simvastatin concentration gradient, corrected for Trikafta-induced baseline swelling. d) AUC values for R334W/R334W and F508del/F508del PDIOs upon simvastatin and mevastatin treatment, with respectively VX-770 and VX-770/VX-809 as background (all at 3 µM). Means are shown of three biological replicate experiments with three technical replicates per condition; sem is indicated by error bars.