Validation of the top hits (FK228, chaetocin, LAQ824, and largazole homodimer) in organoids derived from a clinically relevant KC mouse model confirmed that ADM can be reversed without inducing significant cytotoxicity even in the presence of mutant Kras. Our findings demonstrate a unique mechanism of action for epigenetic compounds and suggest that the phenotypic screen developed here may be applied to discover potential new treatments for PDAC. This evidence concerns the gene KRAS and keratoconus.