Figure 1.
Screening strategy, compound triage, and potency and maximum efficacy improvements during optimization of PTI-CH. (A) The screening funnel showing the steps used to confirm and characterize compound hits from the small-molecule library. (B) The number of compounds at the beginning and end of each of the triage steps in the screening process. The common pharmacophore for PTI-CA and PTI-CH is shown, with R1-3 and Ra side groups as described.20 (C) The yellow fluorescent protein (YFP) fluorescence quenching in response to sodium iodide (NaI) addition is shown for the DMSO control wells from one plate (±5 standard deviations) in comparison to the three indicated reference compounds that were included as test compounds in single wells in the compound library. These same reference compounds were also present on each plate in control wells (see text). CFTR, cystic fibrosis transmembrane conductance regulator; HBE, human bronchial epithelial; HTS, high-throughput screen.