Fig. 1. AL101 inhibits NOTCH activation and cell viability in a NOTCH1-mutated ACC organoid but not in NOTCH wild-type ACC cell lines.
A Hierarchical clustering of normalized baseline expression of 21 NOTCH-related genes in an organoid bearing NOTCH1 activating mutations and three ACC cell lines with wild-type NOTCH genes displayed as a heatmap. Higher or lower expression of genes is indicated with shades of red or blue cells, respectively. B In vitro ACC cell models were treated with increasing concentrations of AL101 and relative cell viability was determined on day 14. *p < 0.05, **p < 0.01, and ***p < 0.001. C Normalized expression of 21 NOTCH-related genes in the ACC in vitro cell models treated with increasing concentrations of AL101 displayed as a heatmap. Higher or lower expression of genes is indicated with shades of red or blue cells, respectively. D NOTCH activation caller plot scores the level of NOTCH signaling activity in the indicated samples by using ssGSEA (axis Y) and kTSP (axis X) algorithms on a set of NOTCH-related genes, where a shift down and to the left indicates reduced NOTCH signaling activity.