Figure 1.
Discovery of ΔF508-CFTR correctors by high-throughput screening. (A) Screening procedure. FRT cells coexpressing ΔF508-CFTR and a halide-sensitive YFP were incubated with test compounds (10 μM) at 37°C. ΔF508-CFTR function was assayed at 18–24 hours in a plate reader according to YFP fluorescence quenching by iodide in the presence of forskolin (20 μM) plus genistein (fsk + gen) (50 μM). (B) Representative traces showing iodide influx under control conditions (37°C) or after 24 hours incubation at 27°C or with 4-PBA (4 mM) or correctors (10 μM; 37°C). (C) Chemical structures of correctors of 4 chemical classes. See Supplemental Table 1 for full listing of correctors and their activities. (D) Dose-response data for indicated correctors (SEM; n = 5). The dashed line indicates the level of activity of the low-temperature rescue used as a positive control.