Description
Brequinar sodium (96201-88-6) is an inhibitor of dihydroorotate dehydrogenase (DHODH)1,2?with IC50’s between 0.2 and 5.8 μM in various cell lines3?and 20 nM in isolated enzyme4. It reduced leukemic cell burden, decreased levels of leukemia-initiating cells, and improved survival in human and mouse models of acute myeloid leukemia.4?Brequinar displayed broad antiviral activity against flaviviruses, positive-strand RNA alphaviruses, negative-strand RNA rhabdoviruses, Influenza A and B viruses, and HIV.5-7
Definition
ChEBI: Brequinar sodium is an organic sodium salt of brequinar. It has a role as an anticoronaviral agent, an antineoplastic agent, an antiviral agent, an EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor, an immunosuppressive agent, a pyrimidine synthesis inhibitor and an antimetabolite. It contains a brequinar(1-).
References
1) Chen?et al.?(1986)?Mechanism of action of the novel anticancer agent 6-fluoro-2-(2’-fluoro-1,1’-biohenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid sodium salt (NSC 368390): inhibition of de novo pyrimidine nucleotide biosynthesis;?Cancer Res.,?46?5014
2) Peters?et al.?(1990)?In vivo inhibition of the pyrimidine de novo enzyme dihydroorotic aicd dehydrogenase by brequinar sodium (DUP-785; NSC 368390) in mice and patients;?Cancer Res.,?50?4644
3) De Kant?et al.?(1989) The relation between inhibition of cell growth and of dihydroorotic acid dehydrogenase by brequinar sodium; Cancer Lett.,?46?123
4) Sykes?et al.?(2016)?Inhibition of Dihydroorotate Overcomes Differentiation Blockade in Acute Myeloid Leukemia;?Cell,?167?171
5) Qing?et al. (2010)?Characterization of Dengue Virus Resistance to Brequinar in Cell Culture;?Antimicrob. Agents Chemother.,?54?3686
6) Andersen?et al.?(2019)?Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine;?Viruses,?11?E964
7) Park?et al.?(2020)?Identification and Characterization of Novel Compounds with Broad-Spectrum Antiviral Activity against Influenza A and B Viruses;?J. Virol.,?94?e02149