Fig. 7: Combinatorial approach with ABBV-075 and BRG1 inhibition shows synergistic effects for H3.3K27M DIPG treatment.

a Indicated DIPG cells were treated with JQ1 and ABBV-075 with a series of concentrations for 72 hours (left). Viability of indicated cells treated with JQ1 (300 nM) and ABBV-075 (60 nM) for the number of days indicated (n = 3 independent experiments) (right). b Neural sphere formation and quantification of the TT150630, TT150714, and PPC cells treated with 0.1% DMSO, 300 nM JQ1, or 60 nM ABBV-075 for 10 days. N = 3 independent experiments. Scale bars: 1 mm. c, d The bioluminescence activity (c) was plotted with representative bioluminescence images (d) and the statistical difference between saline and ABBV-075 treatment groups from animals implanted with TT150630 cells (n = 5 mice in each group). e Kaplan-Meier analysis from animals implanted with TT150630 cells with saline or ABBV-075 treatment (n = 5) in the pons. f Cell viability matrix for DIPG17 and TT150714 DIPG cells treated with distinct ABBV-075 (y-axis) and BRM014 (x-axis) ranging from 0 to 1000 nmol/L (n = 3 independent experiments). g, h The data obtained in f were used to calculate the combination index (CI) values using Chou-Talalay via CompuSyn (g) or Bliss synergy (h) analysis and showed in heatmap matrix (CI < 1, =1, and >1 indicates synergism, addictive, and antagonism, respectively. Bliss score > 10 represents a strong synergism) (n = 3 independent experiments), representative heatmaps were shown in (g) and (h). Data presented as mean ± s.e.m. of three independent experiments (a and b) or mean ± s.e.m. (c), statistical significance was determined by a two-tailed unpaired Student’s t-test (a, b, and c) or log-rank test (e). Experiments were repeated three times independently with similar results (f and g). Source data are provided as a Source Data file.