Brequinar (sodium salt)

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 (EC50s = ~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, monosodium salt. CAS Number: 96201-88-6. Synonyms: DuP-785, NSC 368390. Molecular Formula: C23H14F2NO2 . Na. Formula Weight: 397.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 2 mg/ml, DMSO: 2 mg/ml, Ethanol: 2 mg/ml. lambdamax: 262 nm. SMILES: O=C(C1=C(C)C(C2=CC=C(C3=C(F)C=CC=C3)C=C2)=NC4=C1C=C(C=C4)F)[O-].[Na+]. InChi Code: InChI=1S/C23H15F2NO2.Na/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),/q,+1/p-1. InChi Key: PZOHOALJQOFNTB-UHFFFAOYSA-M.