Aiming to add new small-molecule compoundsto the existing classesof CFTR potentiators, expanding the portfolio of modulators availableto CF patients, we embarked on a drug discovery effort to the identificationof novel chemotypes endowed with a promising pharmacological profile.After a high-throughput screening (HTS) campaign, few structurallydiverse small-molecule hits were identified; among them, the mostpromising ones shared the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (or 1,2,3,4-tetrahydro-γ-carboline) corestructure. This evidence concerns the gene CFTR and cystic fibrosis.