PTC299 and DNA-demethylating agents exert synergistic cytotoxic effects. (A) Summary of CC₅₀ of PTC299 in AML and MDS cell lines. (B) CC₅₀ plots of MDS and AML cells. Cells were treated with the indicated concentrations of PTC299 for 7 days in triplicate. CC₅₀ was defined as the concentration required to reduce cell viability by 50%. Cell viability was determined by MTS assays. (C-E) MTS assays showing the viability of MDS cells treated with the indicated doses of (C) PTC299 and decitabine (DAC), (D) PTC299 and azacitidine (AZA), and (E) PTC299 and brequinar (BRQ) relative to the untreated control. Data are shown as mean ± SD (n = 3). Combination indexes (CI) are shown in the lower panel of each graph.