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Brequinar (DUP-785; NSC368390):Front Pharmacol. 2022 May 5;13:868830 | https://doi.org/10.3389/fphar.2022.868830
"]Purity: ≥98%
Brequinar (formerly DUP-785; NSC-368390), a synthetic quinolinecarboxylic acid analog, is a novel and potent inhibitor of dihydroorotate dehydrogenase with potent activities against a broad spectrum of viruses and 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.
| ln Vitro |
Brequinar has a 17 nM EC50 and decreases the formation of virus progeny by over 90%. Additionally, other orthopoxviruses are inhibited and virus DNA replication is blocked by Brequinar (5 μM). Brequinar has a strong effect on the late stage of the virus cycle, although it has no influence on the expression of early virus genes[1]. Brequinar, which has an EC50 of 78 nM in the CFI test, decreases the amount of envelope protein synthesis and the viral titer in a dose-dependent manner. Brequinar (5 μM) prevents the synthesis of viral RNA. Brequinar has an antiviral action, however pyrimidine neutralizes it. In cell culture, viruses resistant to brequinar can be chosen. Both the WT and NS5 mutant replicons' luciferase activity are suppressed by bequinar (5 μM)[2]. PyNTP rise is successfully inhibited by brequinar sodium. Brequinar sodium has an IC50 of 0.26 μM, which substantially suppresses cell proliferation. Brequinar sodium inhibits p56lck autophosphorylation with an IC50 of 70 μM; the corresponding inhibition values for 25, 50, and 100 μM of Brequinar sodium are 39, 41, and 60%. Additionally, at an IC50 of 70 μM, bequinar sodium prevents the phosphorylation of histone 2B, the exogenous substrate, by p56lck; at 25, 50, 100, and 200 μM, the inhibition is 10, 43, 59, and 86%. The Brequinar Brequinar sodium has an IC50 of 105 μM, which suppresses autophosphorylation of p59fyn by 0, 17, 48, and 65% at 25, 50, 100, and 200 μM, respectively. Moreover, at an IC50 of 20 μM, Brequinar sodium suppresses the phosphorylation of histone 2B by p59fyn; at 10, 25, 50, 100, and 200 μM, the corresponding inhibitions are 26, 54, 79, 83, and 84%[3].
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| ln Vivo |
Compared to untreated BALB/c mice, mice treated with Brequinar sodium (10–20 mg/kg/day) exhibited a 31% decrease in the percentage of packed cell volume. In bone marrow cells, brequinar sodium lowers UTP and CTP levels by 30 and 25%, respectively. When uridine (1000–2000 mg/kg/day) and bequinar sodium (10–20 mg/kg/day) are taken together, anemia is avoided and the hematocrit levels stay at values (61-63%) that are similar to those of untreated controls [3].
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| References |
[1]. Schnellrath LC, et al. Potent antiviral activity of brequinar against the emerging Cantagalo virus in cell culture. Int J Antimicrob Agents. 2011 Nov;38(5):435-41.
[2]. Qing M, et al. Characterization of dengue virus resistance to brequinar in cell culture. Antimicrob Agents Chemother. 2010 Sep;54(9):3686-95. [3]. Xu X, et al. In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium. J Immunol. 1998 Jan 15;160(2):846-53. [4]. Zeping Zuo, et al. Bifunctional Naphtho[2,3-d][1,2,3]triazole-4,9-dione Compounds Exhibit Antitumor Effects In Vitro and In Vivo by Inhibiting Dihydroorotate Dehydrogenase and Inducing Reactive Oxygen Species Production. J Med Chem. 2020 Jun 4. [5]. David C Schultz, et al. Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2. Nature. 2022 Feb 7 |
| Molecular Formula |
C23H15F2NO2
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| Molecular Weight |
375.3675
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| CAS # |
96187-53-0
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| Related CAS # |
Brequinar sodium;96201-88-6
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| SMILES |
O=C(C1=C(C)C(C2=CC=C(C3=CC=CC=C3F)C=C2)=NC4=CC=C(F)C=C14)O
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| Chemical Name |
6-fluoro-2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid
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| Synonyms |
Brequinar; Bipenquinate; DUP 785; NSC368390; DUP785; DUP-785; NSC 368390; DUP785; NSC-368390;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~66.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.54 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6640 mL | 13.3202 mL | 26.6404 mL | |
| 5 mM | 0.5328 mL | 2.6640 mL | 5.3281 mL | |
| 10 mM | 0.2664 mL | 1.3320 mL | 2.6640 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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