To identify cancer cell types that are sensitive to PTC299, a panel of 240 tumor cell lines was tested against which the concentration of compound required to reduce cell viability by 50% (CC50) was determined. Overall, the viability of 18% of cells from solid tumor(34/184) and ~57% of cells from hematologic malignancies (32/56) was reduced with a CC50 of 2 µM or less. Fresh blood from AML patients was treated ex vivo with PTC299 and analyzed by flow cytometry. In these samples, AML cells differentiated as shown by increased monocyte markers (e.g. CD14) or showed reduced viability as shown by a reduction in the blast population. PTC299 reduced the growth of leukemia cells in mouse models using human cell lines or patient-derived xenografts (PDX models). In combination, PTC299 enhanced the activity of various cytotoxic agents in animal models of solid tumor and leukemia. Consistent with the activity of PTC299 as a DHODH inhibitor, patients treated with PTC299 in clinical studies showed increased levels of dihydroorotate, the substrate of DHODH, were observed in serum samples from PTC299-treated patients.