Brequinar
(Synonyms: 布喹那,DUP785; NSC 368390) 目录号 : GC19082
布喹那（Brequinar）是一种特异性的二氢乳清酸脱氢酶DHODH抑制剂，在体外IC50值约为20nM。
Cas No.:96187-53-0
Sample solution is provided at 25 µL, 10mM.
Brequinar is a specific inhibitor of dihydroorotate dehydrogenase DHODH, with an IC50 value of approximately 20nM in vitro [1]. DHODH is an enzyme in the de novo pyrimidine biosynthesis pathway. Buquina's mechanism of action is to target viral DNA synthesis by inhibiting DHODH activity and depleting the cellular pyrimidine pool [2].
In vitro, Buquina (0-75μM) treated BSC-40 cells infected with CTGV virus for 24 hours, significantly inhibiting the intracellular CTGV virus production in a dose-dependent manner, with an EC50 of 0.017±0.05μM, and could be inhibited at a high concentration of 75μM. Ensure that cell viability is maintained at nearly 80%[2]. Buquina (0-25μM) treated Vero cells infected with DENV-2, WNV, YFV, PWV, and WEEV viruses for 42 hours, effectively inhibiting all tested viruses, and the antiviral activity was not caused by compound-mediated toxicity [3]. Buquinar (0-100 μM) treated IBRS-2 cells infected with FMDV for 8 hours and effectively inhibited the protein and mRNA expression of FMDV [4].
In vivo, Buquina (50μg) treated FMDV-infected suckling mice (body weight 3-4g) through intraperitoneal injection, significantly prolonging the survival time of suckling mice and reducing the lesions of cardiac tissue [4]. Buquina (10-20 mg/kg) was treated with BALB/c mice through intraperitoneal injection, causing a 31% reduction in blood cell accumulation volume percentage, and a 30% and 25% reduction in UTP and CTP levels in bone marrow cells, respectively, indicating that Buquina Quinal treatment of mice may induce anemia [5].
References:
[1] Sykes D B , Kfoury Y S , Mercier F ,et al.Inhibition of the Enzyme Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia[J].Blood, 2016, 128(22):1656-1656.
[2] Schnellrath L C , Damaso C R .Potent antiviral activity of brequinar against the emerging Cantagalo virus in cell culture[J].International journal of antimicrobial agents, 2011, 38(5):435-441.
[3] Qing M , Zou G , Wang Q Y ,et al.Characterization of dengue virus resistance to brequinar in cell culture.[J].Antimicrobial Agents and Chemotherapy, 2010, 54(9):3686-3695.
[4] Li S F , Gong M J , Sun Y F ,et al.Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo[J].Biomedicine & pharmacotherapy, 2019, 116:108982.
[5] Xu X , Williams J W , Shen J ,et al.In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium.[J].Journal of Immunology, 1998, 160(2):846-53.
布喹那（Brequinar）是一种特异性的二氢乳清酸脱氢酶DHODH抑制剂，在体外IC50值约为20nM[1]。DHODH是嘧啶从头生物合成途径的一种酶，布喹那的作用机制是通过抑制DHODH活性，耗尽细胞嘧啶池来靶向病毒DNA合成[2]。
在体外，布喹那（0-75μM）处理受CTGV病毒感染的BSC-40细胞24h，以剂量依赖性方式显著抑制胞内CTGV病毒产量，EC50为0.017±0.05μM，且在高浓度75μM时能保证细胞活力保持在近80%[2]。布喹那（0-25μM）分别处理受DENV-2, WNV, YFV, PWV, WEEV病毒感染的Vero细胞42h，有效抑制所有测试的病毒，且抗病毒活性并非由化合物介导的毒性引起[3]。布喹那（0-100μM）处理感染FMDV的IBRS-2细胞8h，有效抑制FMDV的蛋白和mRNA表达[4]。
在体内，布喹那（50μg）通过腹腔注射治疗受FMDV感染的乳鼠（体重3-4g），显著延长了乳鼠的存活时间，减轻了心脏组织的病变[4]。布喹那（10-20 mg/kg）通过腹腔注射处理BALB/c小鼠，引起血细胞堆积体积百分比减少了31%，骨髓细胞中的UTP和CTP水平分别降低了30%和 25%，说明布喹那治疗小鼠可能会诱发贫血[5]。
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Kinase experiment [1]: |
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Preparation method |
Immunoprecipitated p59fyn or p56lck from CTLL-4 cells or LSTRA cells (5×106) was preincubated with various concentrations of Brequinar(0-200μM) in the PTK buffer on ice for 10 min. Exogenous substrate, histone 2B (2μg), was added and, after 10 min, the reaction was initiated by addition of 10 μCi [γ-32P]ATP. After incubation at 20°C for 10 min, the reaction mixture was subjected to electrophoresis in a 12.5% SDS-polyacrylamide gel. Phosphorylation of the kinase and the exogenous substrate was analyzed by autoradiography. |
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Reaction Conditions |
0-200μM; |
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Applications |
Brequinar inhibited autophosphorylation of p56lck with an IC50 of 70 μM; Brequinar inhibited autophosphorylation of p59fyn with an IC50 of 105 μM; Brequinar also inhibited the phosphorylation by p59fyn of histone 2B with an IC50 of 20 μM. |
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Cell experiment [2]: |
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Cell lines |
Vero cells |
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Preparation method |
Spectrum of Brequinar antiviral activity. Vero cells were infected with the indicated viruses at an MOI of 0.1; the infected cells were immediately treated with Brequinar(0-25μM). For DENV-2, WNV, YFV, PWV, and WEEV, culture media were collected at 42 h p.i. and viral titers were measured using plaque assays. |
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Reaction Conditions |
0-25μM; 42h |
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Applications |
Brequinar effectively inhibited all viruses tested and antiviral activity was not due to compound-mediated toxicity. |
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Animal experiment [3]: |
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Animal models |
Specific-pathogen-free suckling mice |
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Preparation method |
Specific-pathogen-free suckling mice, 3 to 4 days old, weighing 3 to 4g. Suckling mice were inoculated by intraperitoneal injection with 50 μg of Brequinar. Mice were treated with PBS containing 10% DMSO and 5% Tween-80 in the same volume as controls. Two hours following Brequinar injection, the suckling mice were challenged with 100 LD50 FMDV in a volume of 100 μL by intraperitoneal injection. The animals were monitored for 5 days. |
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Dosage form |
50μg; i.p. |
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Applications |
Brequinar significantly prolonged the survival time of infected suckling mice. Brequinar treatment significantly alleviated lesions in the heart tissue of FMDV-infected mice. |
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References: [1] Xu X , Williams J W , Shen J ,et al.In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium.[J].Journal of Immunology, 1998, 160(2):846-53. [2] Qing M , Zou G , Wang Q Y ,et al. Characterization of dengue virus resistance to brequinar in cell culture.[J].Antimicrobial Agents and Chemotherapy, 2010, 54(9):3686-3695. [3]Li S F , Gong M J , Sun Y F ,et al.Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo[J].Biomedicine & pharmacotherapy , 2019, 116:108982. |
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| Cas No. | 96187-53-0 | SDF | |
| 别名 | 布喹那,DUP785; NSC 368390 | ||
| Canonical SMILES | O=C(C1=C(C)C(C2=CC=C(C3=CC=CC=C3F)C=C2)=NC4=CC=C(F)C=C14)O | ||
| 分子式 | C23H15F2NO2 | 分子量 | 375.37 |
| 溶解度 | DMSO : 35.71 mg/mL (95.13 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.664 mL | 13.3202 mL | 26.6404 mL |
| 5 mM | 0.5328 mL | 2.664 mL | 5.3281 mL |
| 10 mM | 0.2664 mL | 1.332 mL | 2.664 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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