Fig. 1

Cell viability screen to identify compounds targeting epigenetic regulators that synergize with MS023. a Scheme of the method used to measure synergy of MS023 with drugs from the Epigenetic/Anticancer compound library. Plates were seeded (20 K cells/well) and treated the next day with MS023 or DMSO. Drugs from the Epigenetic/Anticancer compound library were added on the following day. On day 3, viability was analyzed by flow cytometry using Guava® ViaCount™ Reagent. b Cell viability of A549 cells treated with DMSO (blue) or MS023 16.5 µM (red) through the screen. Cell viability was expressed as a percentage relative to DMSO-treated cells. Treatment with MS023 significantly (p = 0.0034 Wilcoxon matched-pairs signed rank test) decreased cell viability by 23% between vehicle condition (DMSO: 100.0 ± 3.3; n = 12) and MS023 treatment (77.3 ± 5.2; n = 11). c Drug screening results showing the distribution of viability of A549 cells after treatment with the drug library in monotherapy (10 µM, 24 h) or with a 24 h pre-treatment with MS023 (16.5 µM). Each dot represents cell viability (%) of a compound for each condition (monotherapy vs combination with MS023) relative to vehicle treated cells. Mean viability is significantly decreased by 23% (77.2 ± 16.4 vs. 54.2 ± 19.4; unpaired, nonparametric, Mann–Withney analysis, p < 0.001) indicating a global effect of MS023 pre-treatment on cell viability. For this representation, 3 drugs (CX-6258-HCL; Pirarubicin; MC1568) produced 1% cell viability and were excluded for the analyses in both conditions. d Synergy index obtained after the sequential combination of the MS023 followed by the Epigenetic/Anticancer drug library. A synergy index of 1.12 was set as a threshold for all combination to be considered synergistic