Identification of perhexiline as a Hes1-signature modulator drug. (A) Top Connectivity Map analysis hits for drugs with signatures overlapping with those induced by Hes1 knockout in NOTCH1-induced T-ALL. (B) Structure of perhexiline. (C) Western blot analysis of HES1 expression in CUTLL1 cells treated with perhexiline. (D) Heat map representation of the top 50 differentially expressed genes (P < .0001) between vehicle-treated and perhexiline-treated CUTLL1 cells. The scale bar shows color-coded differential expression, with red indicating higher levels and blue indicating lower levels of expression. (E) GSEA analysis plots of genes upregulated and downregulated on Hes1 knockout in mouse NOTCH1-induced T-ALL cells in the expression signature induced by perhexiline treatment. (F) GSEA analysis plots of genes upregulated and downregulated on perhexiline treatment in CUTLL1 cells in the expression signature induced by Hes1 knockout in mouse NOTCH1-induced T-ALL cells and in the expression signature induced by HES1 shRNA knockdown in CUTLL1 cells.