Chemical structures of small-molecule CFTR inhibitors. Top: original (pre-high–throughput screening) CFTR inhibitors. Center: absorbable CFTR inhibitors acting at the CFTR cytoplasmic surface. Bottom: externally acting hydrazide-class CFTR inhibitors. BPO, benzopyrimido-pyrrolo-oxazine-dione; CFTR, cystic fibrosis transmembrane conductance regulator; DPC, diphenylamine-2-carboxylate; NPPB, 5-nitro-2-(3-phenylpropyl-amino)benzoate; PPQ, pyrimido-pyrrolo-quinoxalinedione.