Rescuing of F508del-CFTR traffic by RDR01752 is not additive to VX-809 or VX-661
Next, we tested whether rescuing by RDR01752 is additive to that of other correctors, namely FDA-approved drugs VX-809 and VX-661 (Fig. 5) or C18 (Fig. S2). We also evaluated whether chronic exposure to VX-770 affects the rescue of F508del-CFTR by RDR01752 (Figs. 5 and S2). CFBE cells stably expressing mCherry-Flag-F508del-CFTR were incubated with each corrector for 48h and CFTR PM levels were quantified as above. None of the two-corrector combinations further enhance F508del-CFTR PM expression compared to each corrector alone (Fig. 5). Similarly to VX-809 or VX-661, rescue of F508del-CFTR by RDR01752 under chronic exposure to a relatively high concentration of VX-770 resulted in a decrease of F508del-CFTR PM expression (Fig. S2). The inhibitory effect of chronic exposure to VX-770 on F508del-CFTR rescue by VX-809 or VX-661 exposure observed here, as previously reported by others (Cholonet al., 2014; Veit et al., 2014), was even more pronounced for any combination of two correctors.