WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205953
CAS#: 96187-53-0 (free acid)
Description: Brequinar is a dihydroorotate dehydrogenase inhibitor (DHODH inhibitor) with antineoplastic properties. Brequinar inhibits the enzyme dihydroorotate dehydrogenase, thereby blocking de novo pyrimidine biosynthesis. This agent may also enhance the in vivo antitumor effect of antineoplastic agents such as 5-FU. The in vitro study shows that Brequinar potently inhibited EV71, EV70, and CVB3 replication at 50% inhibitory concentration (IC50) of 82.40 nM, 29.26 nM, and 35.14 nM, respectively. Brequinar targeted virus DNA synthesis by depleting the cellular pyrimidine pool, which was bypassed by the salvage pathway when URD was added to the cell cultures.
Hodoodo Cat#: H205953
Name: Brequinar
CAS#: 96187-53-0 (free acid)
Chemical Formula: C23H15F2NO2
Exact Mass: 375.11
Molecular Weight: 375.370
Elemental Analysis: C, 73.59; H, 4.03; F, 10.12; N, 3.73; O, 8.52
Related CAS #: 96201-88-6 (sodium) 96187-53-0 (free acid) Brequinar sodium hydrate
Synonym: Brequinar; Bipenquinate; DUP 785; DUP785; DUP-785; NSC 368390; NSC-368390; NSC368390.;
IUPAC/Chemical Name: 6-fluoro-2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid
InChi Key: PHEZJEYUWHETKO-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(C1=C(C)C(C2=CC=C(C3=CC=CC=C3F)C=C2)=NC4=CC=C(F)C=C14)O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Brequinar (DUP785) is a potent inhibitor of dihydroorotate dehydrogenase (DHODH) with an IC50 of 5.2 nM for human DHODH. |
| In vitro activity: | Brequinar potently inhibited EV71 replication in a dose-dependent manner as measured in both RNA and protein levels (Figure 1A and 1D), although low concentrations (0.01~0.1 μM) of Brequinar slightly enhanced EV71 replication. Reference: Am J Transl Res. 2020; 12(12): 8247–8255. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791496/ |
| In vivo activity: | As shown in Fig. 7, BQR (brequinar) treatment significantly alleviated lesions in the heart tissue of FMDV-infected mice (P |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 25.9 | 70.00 |
The following data is based on the product molecular weight 375.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Fu H, Zhang Z, Dai Y, Liu S, Fu E. Brequinar inhibits enterovirus replication by targeting biosynthesis pathway of pyrimidines. Am J Transl Res. 2020 Dec 25;12(12):8247-8255. PMID: 33437396; PMCID: PMC7791496. 2. 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. Epub 2019 May 27. PMID: 31146110. |
| In vitro protocol: | 1. Fu H, Zhang Z, Dai Y, Liu S, Fu E. Brequinar inhibits enterovirus replication by targeting biosynthesis pathway of pyrimidines. Am J Transl Res. 2020 Dec 25;12(12):8247-8255. PMID: 33437396; PMCID: PMC7791496. 2. 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. Epub 2019 May 27. PMID: 31146110. |
| In vivo protocol: | 1. 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. Epub 2019 May 27. PMID: 31146110. |
1: Horvat NK, Lesinski GB. Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells. J Clin Invest. 2022 Dec 1;132(23):e165506. doi: 10.1172/JCI165506. PMID: 36453548; PMCID: PMC9711868.
2: Khairy A, Hammoda HM, Celik I, Zaatout HH, Ibrahim RS. Discovery of potential natural dihydroorotate dehydrogenase inhibitors and their synergism with brequinar via integrated molecular docking, dynamic simulations and in vitro approach. Sci Rep. 2022 Nov 9;12(1):19037. doi: 10.1038/s41598-022-23006-1. PMID: 36351991; PMCID: PMC9646789.
3: Demarest JF, Kienle M, Boytz R, Ayres M, Kim EJ, Patten JJ, Chung D, Gandhi V, Davey RA, Sykes DB, Shohdy N, Pottage JC Jr, Kumar VS. Brequinar and dipyridamole in combination exhibits synergistic antiviral activity against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19. Antiviral Res. 2022 Oct;206:105403. doi: 10.1016/j.antiviral.2022.105403. Epub 2022 Aug 28. PMID: 36041646; PMCID: PMC9420051.
4: Grigoryan R, Arabyan E, Izmailyan R, Karalyan Z, Jordão N, Ferreira F, Zakaryan H. Antiviral activity of brequinar against African swine fever virus infection in vitro. Virus Res. 2022 Aug;317:198826. doi: 10.1016/j.virusres.2022.198826. Epub 2022 May 23. PMID: 35618075.
5: Fu H, Zhang Z, Dai Y, Liu S, Fu E. Brequinar inhibits enterovirus replication by targeting biosynthesis pathway of pyrimidines. Am J Transl Res. 2020 Dec 25;12(12):8247-8255. PMID: 33437396; PMCID: PMC7791496.
6: Cuthbertson CR, Guo H, Kyani A, Madak JT, Arabzada Z, Neamati N. The Dihydroorotate Dehydrogenase Inhibitor Brequinar Is Synergistic with ENT1/2 Inhibitors. ACS Pharmacol Transl Sci. 2020 Nov 23;3(6):1242-1252. doi: 10.1021/acsptsci.0c00124. PMID: 33344900; PMCID: PMC7737209.
7: DeRatt LG, Christine Pietsch E, Tanner A, Shaffer P, Jacoby E, Wang W, Kazmi F, Zhang X, Attar RM, Edwards JP, Kuduk SD. A carboxylic acid isostere screen of the DHODH inhibitor Brequinar. Bioorg Med Chem Lett. 2020 Nov 15;30(22):127589. doi: 10.1016/j.bmcl.2020.127589. Epub 2020 Sep 29. PMID: 33007394.
8: 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):964. doi: 10.3390/v11100964. PMID: 31635418; PMCID: PMC6832696.
9: 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. Epub 2019 May 27. PMID: 31146110.
10: 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. Epub 2019 Jan 19. PMID: 30663496.
11: Dorasamy MS, Ab A, Nellore K, Wong PF. Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin. Biomed Pharmacother. 2019 Feb;110:29-36. doi: 10.1016/j.biopha.2018.11.010. Epub 2018 Nov 17. PMID: 30458345.
12: Madak JT, Cuthbertson CR, Chen W, Showalter HD, Neamati N. Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition. Chemistry. 2017 Oct 9;23(56):13875-13878. doi: 10.1002/chem.201702999. Epub 2017 Sep 12. PMID: 28833638.
13: He T, Haapa-Paananen S, Kaminskyy VO, Kohonen P, Fey V, Zhivotovsky B, Kallioniemi O, Perälä M. Inhibition of the mitochondrial pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase by doxorubicin and brequinar sensitizes cancer cells to TRAIL-induced apoptosis. Oncogene. 2014 Jul 3;33(27):3538-49. doi: 10.1038/onc.2013.313. Epub 2013 Sep 9. PMID: 24013224.
14: Schnellrath LC, Damaso CR. Potent antiviral activity of brequinar against the emerging Cantagalo virus in cell culture. Int J Antimicrob Agents. 2011 Nov;38(5):435-41. doi: 10.1016/j.ijantimicag.2011.07.002. Epub 2011 Aug 12. PMID: 21840180.
15: Qing M, Zou G, Wang QY, Xu HY, Dong H, Yuan Z, Shi PY. Characterization of dengue virus resistance to brequinar in cell culture. Antimicrob Agents Chemother. 2010 Sep;54(9):3686-95. doi: 10.1128/AAC.00561-10. Epub 2010 Jul 6. PMID: 20606073; PMCID: PMC2934995.
16: Hurt DE, Sutton AE, Clardy J. Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1610-5. doi: 10.1016/j.bmcl.2005.12.029. Epub 2006 Jan 10. PMID: 16406782.
17: Boa AN, Canavan SP, Hirst PR, Ramsey C, Stead AM, McConkey GA. Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase. Bioorg Med Chem. 2005 Mar 15;13(6):1945-67. doi: 10.1016/j.bmc.2005.01.017. PMID: 15727850.
18: McLean JE, Neidhardt EA, Grossman TH, Hedstrom L. Multiple inhibitor analysis of the brequinar and leflunomide binding sites on human dihydroorotate dehydrogenase. Biochemistry. 2001 Feb 20;40(7):2194-200. doi: 10.1021/bi001810q. PMID: 11329288.
19: Wennberg L, Song Z, Wijkström M, Zhang J, Bari S, Sundberg B, Groth CG, Korsgren O. Brequinar in combination with cyclosporine a inhibits islet xenograft rejection for up to 24 days: a study in the pig-to-rat model. Transplant Proc. 2000 Aug;32(5):1026. doi: 10.1016/s0041-1345(00)01097-6. PMID: 10936333.
20: Knecht W, Henseling J, Löffler M. Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76. doi: 10.1016/s0009-2797(99)00144-1. PMID: 10658902.
