Fig. 5: Profiling of multiple USP7-targeting compounds by DIA ubiquitinomics.

a HCT116 cells were treated with four structurally distinct USP7 inhibitors for 1 h. Shown is a principal component analysis (PCA) of the ubiquitinomics data. b Log2 fold changes (lower left part), density distributions (middle part), and Pearson correlations of significantly regulated K-GG peptide intensities with four different compounds targeting USP7. c Venn diagrams of significantly up- and downregulated K-GG peptides with the different compounds. d Dot plot showing Log2 fold changes (USP7-targeting compound vs DMSO) of K-GG peptides for FT671, FT827, GNE-6640, and GNE-6776. K-GG peptides mapping to USP7 are highlighted. e Fold changes of ubiquitinated peptides (FT671/DMSO, Log2-transformed) for four structurally distinct USP7 inhibitors. Shown are ubiquitin peptide profiles for those proteins that harbor significantly and >2-fold increased ubiquitination sites with three out of four USP7 inhibitors and that are ubiquitinated and degraded upon FT671 treatment (see Fig. 4). Source data are provided as a Source Data file.