Brequinar

Brequinar is an inhibitor of dihydroorotate dehydrogenase (DHODH; IC₅₀ = ~20 nM), the enzyme that converts dihydroorotate to orotate during de novo pyrimidine synthesis.¹ Brequinar is selective for DHODH over a panel of greater than 400 kinases at 100 nM. It induces differentiation of ER-HoxA9, U937, and THP-1 cells in vitro (ED₅₀s = ~1 µM) and of tumor cells in a THP-1 mouse xenograft model when administered at doses of 15 mg/kg three times daily and 5 mg/kg per day. It also reduces tumor growth in THP-1, HL-60, and MOLM-13 mouse xenograft models. In a retroviral transduction mouse model of HoxA9 + Meis1 acute myeloid leukemia (AML), brequinar induces differentiation of bone marrow leukemic cells and increases survival.

WARNING This product is not for human or veterinary use.

1. Sykes, D.B., Kfoury, Y.S., Mercier, F.E., et al. Inhibition of dihydroorotate dehydrogenase overcomes differentiation blockade in acute myeloid leukemia. Cell 167(1), 171-186 (2016).