Fig. 3: Historical but not next-generation KAT inhibitors produce gross injury phenotypes in cell painting.
From: Reference compounds for characterizing cellular injury in high-content cellular morphology assays
A collection of KATIs were each profiled by cell painting (CP) after 24 h of compound exposure in U-2 OS cells. Compared to ngKATIs, many hKATIs are associated with assay interferences, suboptimal specificity, and cytotoxicity. a Most hKATIs but not ngKATIs perturb cell number and are scored as bioactive in CP and occupy different feature-spaces by PCA. The cut-off is 3 SD from the mean of DMSO-treated wells using the CP activity (Mahalanobis distances). b Reduced CP feature summaries for hKATIs and ngKATIs. Several hKATIs can produce CP phenotypes similar to the gross cell injury phenotype (cluster 9), especially at higher compound concentrations. The ngKATIs do not cause as pronounced CP phenotypes as hKATIs. c Select CP profiles of KAT inhibitors. The ngKATIs 468–472 do not cause the gross cellular injury CP phenotype, whereas many hKATIs produce the cell injury CP phenotype at higher compound concentrations. Note the pronounced inverse relationship between relative cell number and CP activity. Image scales: 50 μm. Data are mean ± SD of four intra-run technical replicates each performed on separate microplates. h/ngKATI; historical/next-generation lysine acetyltransferase inhibitor; PC, principal component. Source data are provided as a Source Data file.
