Extended Data Fig. 3 |. Regulation of target proteins informs on compound MOA.

(a) The 541 compound-target pairs analyzed, broken down by the two different regulation thresholds. Those in green and red are highlighted/annotated in Fig. 3c. (b) Proportion of primary targets that were identified, broken down by whether they were quantified in the TMT group that contained the compound. For a fraction of the target-compound pairs (<11%), the target was expressed in HCT116 cells, but it was not quantified in the TMT plex containing the compound. (c) Proportion of all 2,485 annotated targets quantified in the dataset (d) Number of regulated events per compound, separated by those that regulate their target (blue) and those that do not (black). (e) Histogram of Log2 fold change (compound versus DMSO) for all compound-target regulation events. The number of upregulation and downregulation events is indicated. (f) The compound-target regulation event with the smallest fold change is highlighted in purple. The 5 SD threshold is marked with an asterisk. Three HDAC inhibitors also regulate XPO1 expression to similar levels, suggesting a five standard deviation cutoff captures reproducible biology. (g) BRD4 expression across the dataset, with BRD4 inhibitors (purple) and PLK1 inhibitors (red) annotated. This is a low-fold change regulation event, highly reproducible across several compounds of the same class. (h) Protein expression (Log2 fold change) of all quantified proteins for the TYMS inhibitor nolatrexed, (highlighted in Fig. 3d) with DHFR labeled. Compound structure is shown below. (i) Related to Fig. 3f: Expression of the angiomotin family of proteins (AMOT, AMOTL1, and AMOTL2) across the MOA dataset. TNKS inhibitors (purple), PARP inhibitors (red) and proteasome inhibitors (brown) are highlighted. ( j) Expression of several proteins regulated by at least two compounds that target them. In each case the 5 SD threshold is marked with an asterisk.