Figure 3: Z1834339853 binds to the same site as ivacaftor and GLPG1837.

(a) Cryo-EM structure of phosphorylated and ATP-bound CFTR (E1371Q) in complex with ‘853. (b) Zoomed-in views of the density of ‘853 (top) and a comparison between the docked pose (salmon) and the cryo-EM pose (magenta). (c) Representative macroscopic current traces and dose-response curves of fully phosphorylated WT, S308A, and Y304A CFTR in response to perfusion of (S)-’853 onto inside-out excised membrane patches. 3 mM ATP was used. Each data point represents the mean and SEs determined from 3 to 12 patches.