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'''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 [[nucleotide]]s 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.<ref>Cramer DV. Brequinar sodium. ''Pediatr Nephrol''. 1995;9 Suppl:S52-5. {{pmid|749248}}</ref><ref>Peters GJ.Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor. ''Nucleosides Nucleotides Nucleic Acids''. 2018;37(12):666-678. {{doi|10.1080/15257770.2018.1508692}} {{pmid|30663496}}</ref> However it continues to be researched both as part of a potential combination therapy for some cancers,<ref>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}}</ref><ref>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}}</ref> or alternatively as an [[antiparasitic]],<ref>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}}</ref> or [[antiviral]] drug.<ref>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}}</ref><ref>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}}</ref><ref>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}}</ref>
'''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 [[nucleotide]]s 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.<ref name="pmid7492488">{{cite journal | vauthors = Cramer DV | title = Brequinar sodium | journal = Pediatric Nephrology | volume = 9 Suppl | issue = | pages = S52-5 | date = 1995 | pmid = 7492488 | doi = 10.1007/bf00867685 }}</ref><ref name="pmid30663496">{{cite journal | vauthors = Peters GJ | title = Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor | journal = Nucleosides, Nucleotides & Nucleic Acids | volume = 37 | issue = 12 | pages = 666–678 | date = 2018 | pmid = 30663496 | doi = 10.1080/15257770.2018.1508692 }}</ref> However it continues to be researched both as part of a potential combination therapy for some cancers,<ref name="pmid21861807">{{cite journal | vauthors = Vyas VK, Ghate M | title = Recent developments in the medicinal chemistry and therapeutic potential of dihydroorotate dehydrogenase (DHODH) inhibitors | journal = Mini Reviews in Medicinal Chemistry | volume = 11 | issue = 12 | pages = 1039–55 | date = October 2011 | pmid = 21861807 | doi = 10.2174/138955711797247707 }}</ref><ref name="pmid30347213">{{cite journal | vauthors = Madak JT, Bankhead A, Cuthbertson CR, Showalter HD, Neamati N | title = Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer | journal = Pharmacology & Therapeutics | volume = 195 | issue = | pages = 111–131 | date = March 2019 | pmid = 30347213 | doi = 10.1016/j.pharmthera.2018.10.012 }}</ref> or alternatively as an [[antiparasitic]],<ref name="pmid31557612">{{cite journal | vauthors = Boschi D, Pippione AC, Sainas S, Lolli ML | title = Dihydroorotate dehydrogenase inhibitors in anti-infective drug research | journal = European Journal of Medicinal Chemistry | volume = 183 | issue = | pages = 111681 | date = December 2019 | pmid = 31557612 | doi = 10.1016/j.ejmech.2019.111681 }}</ref> or [[antiviral]] drug.<ref name="pmid31146110">{{cite journal | vauthors = Li SF, Gong MJ, Sun YF, Shao JJ, Zhang YG, Chang HY | title = Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo | journal = Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie | volume = 116 | issue = | pages = 108982 | date = August 2019 | pmid = 31146110 | doi = 10.1016/j.biopha.2019.108982 }}</ref><ref name="pmid31635418">{{cite journal | vauthors = 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 | display-authors = 6 | title = Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine | journal = Viruses | volume = 11 | issue = 10 | pages = 964 | date = October 2019 | pmid = 31635418 | pmc = 6832696 | doi = 10.3390/v11100964 }}</ref><ref name="pmid31941776">{{cite journal | vauthors = Park JG, Ávila-Pérez G, Nogales A, Blanco-Lobo P, de la Torre JC, Martínez-Sobrido L | title = Identification and characterization of novel compounds with broad spectrum antiviral activity against influenza A and B viruses | journal = Journal of Virology | volume = | issue = | date = January 2020 | pmid = 31941776 | doi = 10.1128/JVI.02149-19 }}</ref>


==See also==
== See also ==
* [[Teriflunomide]]
* [[Teriflunomide]]
* [[Leflunomide]]
* [[Leflunomide]]

Revision as of 06:18, 13 February 2020

Brequinar
Clinical data
Trade namesBrequinar
Identifiers
  • 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H15F2NO2
Molar mass375.4 g·mol−1
3D model (JSmol)
  • CC1=C(C2=C(C=CC(=C2)F)N=C1C3=CC=C(C=C3)C4=CC=CC=C4F)C(=O)O
  • 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][4] or alternatively as an antiparasitic,[5] or antiviral drug.[6][7][8]

See also

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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  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.
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