ASLAN003 is an inhibitor of dihydroorotate dehydrogenase (DHODH; IC50 = 35 nM).1 It inhibits the proliferation of MOLM-14 and KG-1 acute myeloid leukemia (AML) cells (IC50s = 0.582 and 0.382 ?M, respectively), as well as induces apoptosis in the same cells when used at concentrations of 0.5 and 1 ?M. ASLAN003 (1, 2, and 4 ?M) induces differentiation in bone marrow cells isolated from patients with AML or myelodysplastic syndrome (MDS). It improves survival in a patient-derived xenograft (PDX) mouse model of AML when administered at a dose of 50 mg/kg.
1.Zhou, J., Quah, J.Y., Ng, Y., et al.ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemiaHaematologica105(9)2286-2297(2020)