Fig 1: Analysis of validation screening exercises.a Carbonic anhydrase IX (CAIX) screen output summarized by sum of lower bound (lb) calculated enrichments for all Cy2-Cy3 disynthons with all primary sulfonamide-containing building blocks included in the DOSEDO library shown (summed lower bound enrichments <25 was excluded from the plot for clarity). b Chemical space map generated through UMAP multidimensional scaling of a Tanimoto distance matrix derived from Morgan fingerprints of enumerated encoded compounds. A random sample of 50,000 compounds from the enumerated DOSEDO library was used as background chemical space, along with 44 selected compounds for resynthesis. These compounds are colored by their binding target. c Calculated enrichments of selected resynthesis target compounds from CAIX- and isocitrate dehydrogenase 1 (IDH1) R132H-validation screens. Color scheme as for b. d Structure of 3 alongside differential scanning fluorimetry (DSF) results with N-His-GST (glutathione S-transferase) tagged USP7 as well as His-tagged GST (5 µM) in 50 mM Tris–HCl, pH 7.4. Two peaks belonging to GST (Tm 54.6 °C) and ubiquitin specific peptidase 7 (USP7) (Tm 44.9 °C) were observed in the melt curves of GST-tagged USP7. No thermal stabilization of USP7 by 3 was observed by tracking the USP7 peak; GST stabilization by 3 was observed by tracking the GST peak. 3 induces thermal stabilization of His-tagged GST in a dose-dependent manner, up to 3.3 °C at 100 µM. N = 3 technical replicates. Source data are provided as a Source Data file.