Brequinar

Brequinar is an inhibitor of dihydroorotate dehydrogenase (DHODH, IC50 = ~20 nM), the enzyme that converts dihydroorotate to orotate during de novo pyrimidine synthesis. 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.Formal Name: 6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-methyl-4-quinolinecarboxylic acid. CAS Number: 96187-53-0. Synonyms: NSC 368390. Molecular Formula: C23H15F2NO2. Formula Weight: 375.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 2 mg/ml, DMSO: 5 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 0.2 mg/ml. lambdamax: 252, 324 nm. SMILES: FC1=CC=C2C(C(C(O)=O)=C(C)C(C3=CC=C(C4=C(F)C=CC=C4)C=C3)=N2)=C1. InChi Code: InChI=1S/C23H15F2NO2/c1-13-21(23(27)28)18-12-16(24)10-11-20(18)26-22(13)15-8-6-14(7-9-15)17-4-2-3-5-19(17)25/h2-12H,1H3,(H,27,28). InChi Key: PHEZJEYUWHETKO-UHFFFAOYSA-N.