Brequinar

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][4] or alternatively as an antiparasitic,[5] or antiviral drug.[6][7][8]

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
DrugBank	DB03523
ChemSpider	51422
UNII	5XL19F49H6
KEGG	D03154
ChEMBL	ChEMBL38434
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

See also

• Leflunomide - Clinically used DHODH inhibitor
• Methotrexate - the most widely used pyrimidine synthesis inhibitor

References

1. Cramer DV (1995). "Brequinar sodium". Pediatric Nephrology. 9 Suppl: S52-5. doi:10.1007/bf00867685. PMID 7492488.
2. Peters GJ (2018). "Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor". Nucleosides, Nucleotides & Nucleic Acids. 37 (12): 666–678. doi:10.1080/15257770.2018.1508692. PMID 30663496.
3. Vyas VK, Ghate M (October 2011). "Recent developments in the medicinal chemistry and therapeutic potential of dihydroorotate dehydrogenase (DHODH) inhibitors". Mini Reviews in Medicinal Chemistry. 11 (12): 1039–55. doi:10.2174/138955711797247707. PMID 21861807.
4. Madak JT, Bankhead A, Cuthbertson CR, Showalter HD, Neamati N (March 2019). "Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer". Pharmacology & Therapeutics. 195: 111–131. doi:10.1016/j.pharmthera.2018.10.012. PMID 30347213.
5. Boschi D, Pippione AC, Sainas S, Lolli ML (December 2019). "Dihydroorotate dehydrogenase inhibitors in anti-infective drug research". European Journal of Medicinal Chemistry. 183: 111681. doi:10.1016/j.ejmech.2019.111681. PMID 31557612.
6. Li SF, Gong MJ, Sun YF, Shao JJ, Zhang YG, Chang HY (August 2019). "Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo". Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 116: 108982. doi:10.1016/j.biopha.2019.108982. PMID 31146110.
7. Andersen PI, Krpina K, Ianevski A, Shtaida N, Jo E, Yang J, et al. (October 2019). "Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine". Viruses. 11 (10): 964. doi:10.3390/v11100964. PMC 6832696. PMID 31635418.
8. Park JG, Ávila-Pérez G, Nogales A, Blanco-Lobo P, de la Torre JC, Martínez-Sobrido L (January 2020). "Identification and characterization of novel compounds with broad spectrum antiviral activity against influenza A and B viruses". Journal of Virology. doi:10.1128/JVI.02149-19. PMID 31941776.