Brequinar

Brequinar
Clinical data
Trade names	Brequinar
Identifiers
	IUPAC name 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid;
CAS Number	96187-53-0;
PubChem CID	57030;
CompTox Dashboard (EPA)	DTXSID00242165 ;
Chemical and physical data
Formula	C23H15F2NO2
Molar mass	375.4 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C2=C(C=CC(=C2)F)N=C1C3=CC=C(C=C3)C4=CC=CC=C4F)C(=O)O;
	InChI 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); Key:PHEZJEYUWHETKO-UHFFFAOYSA-N;

Brequinar (DuP-785) is a drug that acts as a potent and selective inhibitor of the enzyme dihydroorotate dehydrogenase. It blocks synthesis of pyrimidine based nucleotides in the body and so inhibits cell growth. It has been investigated as an immunosuppressant for preventing rejection after organ transplant and also as an anti-cancer drug, but was not accepted for medical use in either application largely due to its narrow therapeutic dose range and severe side effects when dosed inappropriately.^[1]^[2] However it continues to be researched both as part of a potential combination therapy for some cancers,^[3] or alternatively as an antiparasitic,^[4] or antiviral drug.^[5]^[6]^[7]

References

^ Cramer DV. Brequinar sodium. Pediatr Nephrol. 1995;9 Suppl:S52-5. PMID 749248
^ Vyas VK, Ghate M. Recent developments in the medicinal chemistry and therapeutic potential of dihydroorotate dehydrogenase (DHODH) inhibitors. Mini Rev Med Chem. 2011 Oct;11(12):1039-55. doi:10.2174/138955711797247707 PMID 21861807
^ Madak JT, Bankhead A 3rd, Cuthbertson CR, Showalter HD, Neamati N. Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer. Pharmacol Ther. 2019 Mar;195:111-131. doi:10.1016/j.pharmthera.2018.10.012 PMID 30347213
^ Boschi D, Pippione AC, Sainas S, Lolli ML. Dihydroorotate dehydrogenase inhibitors in anti-infective drug research. Eur J Med Chem. 2019 Dec 1;183:111681. doi:10.1016/j.ejmech.2019.111681 PMID 31557612
^ Li SF, Gong MJ, Sun YF, Shao JJ, Zhang YG, Chang HY. Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo. Biomed Pharmacother. 2019 Aug;116:108982. doi:10.1016/j.biopha.2019.108982 PMID 31146110
^ Andersen PI, Krpina K, Ianevski A, Shtaida N, Jo E, Yang J, Koit S, Tenson T, Hukkanen V, Anthonsen MW, Bjoras M, Evander M, Windisch MP, Zusinaite E, Kainov DE. Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine. Viruses. 2019 Oct 18;11(10). pii: E964. doi:10.3390/v11100964 PMID 31635418
^ Park JG, Ávila-Pérez G, Nogales A, Blanco-Lobo P, de la Torre JC, Martínez-Sobrido L. Identification and characterization of novel compounds with broad spectrum antiviral activity against influenza A and B viruses. J Virol. 2020 Jan 15. pii: JVI.02149-19. doi:10.1128/JVI.02149-19 PMID 31941776

[1] Cramer DV. Brequinar sodium. Pediatr Nephrol. 1995;9 Suppl:S52-5. PMID 749248

[2] Vyas VK, Ghate M. Recent developments in the medicinal chemistry and therapeutic potential of dihydroorotate dehydrogenase (DHODH) inhibitors. Mini Rev Med Chem. 2011 Oct;11(12):1039-55. doi:10.2174/138955711797247707 PMID 21861807

[3] Madak JT, Bankhead A 3rd, Cuthbertson CR, Showalter HD, Neamati N. Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer. Pharmacol Ther. 2019 Mar;195:111-131. doi:10.1016/j.pharmthera.2018.10.012 PMID 30347213

[4] Boschi D, Pippione AC, Sainas S, Lolli ML. Dihydroorotate dehydrogenase inhibitors in anti-infective drug research. Eur J Med Chem. 2019 Dec 1;183:111681. doi:10.1016/j.ejmech.2019.111681 PMID 31557612

[5] Li SF, Gong MJ, Sun YF, Shao JJ, Zhang YG, Chang HY. Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo. Biomed Pharmacother. 2019 Aug;116:108982. doi:10.1016/j.biopha.2019.108982 PMID 31146110

[6] Andersen PI, Krpina K, Ianevski A, Shtaida N, Jo E, Yang J, Koit S, Tenson T, Hukkanen V, Anthonsen MW, Bjoras M, Evander M, Windisch MP, Zusinaite E, Kainov DE. Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine. Viruses. 2019 Oct 18;11(10). pii: E964. doi:10.3390/v11100964 PMID 31635418

[7] Park JG, Ávila-Pérez G, Nogales A, Blanco-Lobo P, de la Torre JC, Martínez-Sobrido L. Identification and characterization of novel compounds with broad spectrum antiviral activity against influenza A and B viruses. J Virol. 2020 Jan 15. pii: JVI.02149-19. doi:10.1128/JVI.02149-19 PMID 31941776

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