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A novel in vitro high-content imaging assay for the prediction of drug-induced lung toxicity.


ABSTRACT: The development of inhaled drugs for respiratory diseases is frequently impacted by lung pathology in non-clinical safety studies. To enable design of novel candidate drugs with the right safety profile, predictive in vitro lung toxicity assays are required that can be applied during drug discovery for early hazard identification and mitigation. Here, we describe a novel high-content imaging-based screening assay that allows for quantification of the tight junction protein occludin in A549 cells, as a model for lung epithelial barrier integrity. We assessed a set of compounds with a known lung safety profile, defined by clinical safety or non-clinical in vivo toxicology data, and were able to correctly identify 9 of 10 compounds with a respiratory safety risk and 9 of 9 compounds without a

SUBMITTER: Fitzpatrick PA 

PROVIDER: S-EPMC11324770 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature