Fig. 3: Analysis of SJ3149 activity in a broad range of human cancer cell lines.
a IC50 values of SJ0040 and SJ3149 in a panel of AL cell lines. The data are plotted as the mean ± SEM from three independent experiments. b Scatterplot of the IC50 distribution of SJ3149 in 29 hematologic cell lines. Cell lines were grouped based on their disease subtype. Dots show the mean IC50 value (in nM) as derived from duplicate 9-point dilution series for each cell line. Horizontal solid lines indicate the geometric means, as derived from the independent samples of each group (B-ALL n = 3, CML n = 2, ALCL, n = 2, AML n = 10, T-ALL n = 8, DLBCL n = 4). c SJ3149 IC50 values for the 115 cancer cell lines relative to the panel average IC50. A negative value indicates a below-average IC50 value. Bars are based on the mean IC50 value as derived from duplicate 9-point dilution series for each cell line. Cell lines were grouped and colored based on their tissue of origin. d Volcano plot comparing compound SJ3149 IC50 differences between altered and wild-type cell lines for 38 established cancer genes. The red node indicates significantly higher IC50 in the TP53-altered cell lines. e Volcano plot of Pearson correlations between SJ3149 IC50 values and basal expression levels of 19,146 genes in 99 cell lines. Plots in d and e were generated using 10log IC50 values (in nM) derived from duplicate 9-point dilution series for each cell line. For results in d, the significance of IC50 shifts was determined by two-sided Type II ANOVA as implemented by the ‘Anova()’ function from the ‘car’ package in R. Benjamini–Hochberg multiple testing correction was performed using the ‘p.adjust()’ function from the ‘stats’ package in R. Adjusted p-values < 0.2 were considered significant. For results in e, correlations were determined using the ‘cor.test()’ function from the ‘stats’ package in R, using the Pearson method, pairwise complete observations, and a two-sided alternative hypothesis.
