BAY-2402234 is an inhibitor of dihydroorotate dehydrogenase (DHODH; IC50 = 1.2 nM).1 It induces upregulation of the cell differentiation marker CD11b in MOLM-13 and HEL acute myeloid leukemia (AML) cells (EC50s = 3.16 and 0.96 nM, respectively) and inhibits the proliferation of nine leukemia cell lines (IC50s = 0.08-8.2 nM). BAY-2402234 induces cell cycle arrest at the G2/M phase and apoptosis in TF-1 cells in a concentration-dependent manner. In vivo, BAY-2402234 (1.25, 2.5, and 5 mg/kg) reduces tumor volume in an MV4-11 mouse xenograft model. It also increases survival in patient-derived xenograft (PDX) mouse models of AML.
1.Christian, S., Merz, C., Evans, L., et al.The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignanciesLeukemia33(10)2403-2415(2019)