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Brequinar

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Chemical Structure| 96187-53-0 同义名 : DUP785;NSC 368390
CAS号 : 96187-53-0
货号 : A155500
分子式 : C23H15F2NO2
纯度 : 99%+
分子量 : 375.368
MDL号 : MFCD00866437
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(66.6 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Dihydroorotate dehydrogenase (DHODH) is the only redox enzyme of the six enzymes involved in the de novo biosynthesis pathway. It catalyses the oxidation of dihydroorotate (DHO) to orotate (ORO) and the electrons are transferred via the involvement of two cofactors (flavin mononucleotide (FMN) and either nicotinamide adenine dinucleotide (NAD) or ubiquinone (CoQ)) in the respiratory mitochondrial chain[5]. Brequinar is a potent inhibitor of the mitochondrial DHODH, a rate-limiting enzyme in the pyrimidine de novo nucleotide synthesis. In phase I clinical studies at the maximum tolerated dose (MTD) Brequinar induced a long-term inhibition of DHODH in white blood cells (WBC) and a long-term depletion of plasma uridine[6]. Moreover, combination of Brequinar with doxorubicin resulted in synergistic and additive cell growth inhibition in melanoma cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.32mL

2.66mL

1.33mL

26.64mL

5.33mL

2.66mL
参考文献

[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]Boschi D, Pippione AC, Sainas S, Lolli ML. Dihydroorotate dehydrogenase inhibitors in anti-infective drug research. Eur J Med Chem. 2019;183:111681

[6]Peters GJ. Re-evaluation of Brequinar, a dihydroorotate dehydrogenase inhibitor. Nucleosides Nucleotides Nucleic Acids. 2018;37(12):666-678

[7]Dorasamy MS, Ab A, Nellore K, Wong PF. Synergistic inhibition of melanoma xenografts by Brequinar and Doxorubicin. Biomed Pharmacother. 2019;110:29-36