Fig. 6

Therapeutic potential of hits. A The hit genes in the screen on GU-pBT-7 and GU-pBT-19 were examined with canSAR to predict their druggability. We also did a web-based search for the hits that had commercially available inhibitors. One of the candidates (UBE2N) had a commercial inhibitor (NSC697923), and a dose–response curve for B four CSC and two NSC lines showed that the inhibitor killed all cells at the highest concentration tested (32 µM; n = 3 technical replicates per condition except for the control where n = 12 technical replicates). The ED50 (median effective) was significantly higher in the NSC FT3477 compared to all CSC (* indicates p value < 0.05 in one-sided Welch t test of the ED50). The ED50 was also significantly higher in the H3 wild-type cell lines (GU-pBT-28 and GU-pBT-58) than the H3K27M cell lines (GU-pBT-7 and GU-pBT-19). C Phase images of the CSC GU-pBT-7 (left) and NSC FT3477 (right) with untreated cells (top) and treated with the inhibitor (4 µM) for 4 days. Scale bar = 200 µm