Figure 1.
Identification of novel classes of CFTR inhibitors by high-throughput screening. (A) Screening procedure. FRT cells coexpressing a halide-sensing yellow fluorescent protein (YFP-H148Q) and human wild-type CFTR were incubated with activating cocktail for 15 min before addition of test compounds at 25 μM. Iodide influx was induced by rapid addition of an iodide-containing solution. (B) Structures of novel classes of CFTR inhibitors identified by screening of a collection of 100,000 drug-like small molecules. (C) Dose inhibition of the glycine hydrazide GlyH-101 determined by fluorescence assay (left) and apical Cl− current analysis (right). Apical Cl− current was induced by 100 μM CPT-cAMP. CPT-cAMP and GlyH-101 were added to both apical and basolateral solutions.