Fig. 1: PINCHs precipitate BCL6 in cells and show cell-type-specific viability effects.
From: A pharmacological modality to sequester homomeric proteins
a, Schematic representation of the PINCH mode of action. b, Structures of monovalent ligands and PINCHs that target BCL6. EC50 values are shown in parentheses. c, WB analyses of active BCL6-targeting PINCHs, after 20 h of treatment in Mino cells. Representative results from three independent experiments are shown. Note that we follow the mass of the monomeric BCL6 in WB as, under the harsh sample preparation conditions, the EL221 crosslinked dimer dissociates (Supplementary Fig. 1f–h). d, WB band quantification from n = 3 independent experiments. Data depict the mean and s.d. EC50 curves for individual compounds are shown in Supplementary Fig. 3a. Conc., concentration. e, HEK 293 cells overexpressing BCL6(1–275)–GFP treated with 5 μM parent ligand w8001 (left) and 5 μM EL221 (right). f, Quantification of BCL6–GFP puncta in each treatment. P < 0.0001 in a two-tailed Mann–Whitney test from 223 cells analyzed in two independent experiments. Additional images are shown in Supplementary Fig. 1a. One outlier was removed from the graph for clarity but not from the statistical analysis. Data show the mean values and a 95% confidence interval. g, Viability of different cell lines after 72 h of treatment with EL221, parent ligand w8001 or BCL6-polymerizer BI-3802. Representative results from two independent experimental replicates are shown (n = 6 technical replicates each). Data depict the mean and s.d.
