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Chemical Structure| 21919-05-1 同义名 : -
CAS号 : 21919-05-1
货号 : A509901
分子式 : C9H8N4O5
纯度 : 98%
分子量 : 252.184
MDL号 : MFCD00869490
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(475.84 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 CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is an antitumor prodrug that is activated in certain rat tumors via its 4-hydroxylamine derivative to a potent bifunctional alkylating agent. It is enzymatically activated to generate a difunctional agent, which can form DNA-DNA interstrand crosslinks[2]. The bioactivation of CB 1954 in rat cells involves the aerobic reduction of its 4-nitro group to a 4-hydroxylamine by the enzyme NQO1 (DT-diaphorase)[3].CD-1 nu/nu mice were initially dosed at 200 mol/kg and showed no signs of toxicity, and a higher dose was assessed and the maximum tolerated doses (MTD) was established at 562mol/kg. None of the mice showed overt toxicity at this dose, although weight loss was observed in some animals[4].The formation of CB 1954 metabolites was investigated in the liver, plasma and urine of mice and rats dosed at the respective MTD for 4 h post-dose. In mice dosed at the MTD of 562mol/kg, plasma levels of ALT and AST were raised to 6 and 13 times normal levels, respectively, between 3 and 6 days postdose[5].CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. When compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma[6].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00746590 Hepatocellular Carcinoma Phase 2 Terminated(Study terminated pr... 展开 >>ematurely by sponsor for business reason. One patient was enrolled.) 收起 << - Belgium ... 展开 >> Cliniques Universitaires Saint-Luc Brussels, Belgium, 1200 收起 <<
NCT00746590 - Terminated(Study terminated pr... 展开 >>ematurely by sponsor for business reason. One patient was enrolled.) 收起 << - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.97mL

0.79mL

0.40mL

19.83mL

3.97mL

1.98mL

39.65mL

7.93mL

3.97mL
参考文献

[1]Knox RJ, Jenkins TC, et al. Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy. Cancer Res. 2000;60(15):4179-86.

[2] Knox RJ,et al. Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy. Cancer Res. 2000 Aug 1;60(15):4179-86.

[3] Knox RJ, et al. CB 1954: from the Walker tumor to NQO2 and VDEPT. Curr Pharm Des. 2003;9(26):2091-104.

[4]Cobb, L.M., 1970. Toxicity of the selective antitumor agent 5-aziridino-2,4-dinitrobenzamide in the rat. Toxicol. Appl. Pharmacol. 17, 231–238.

[5] Magdalene Huen Yin Tang,et al. Hepatic nitroreduction, toxicity and toxicokinetics of the anti-tumour prodrug CB 1954 in mouse and rat, Toxicology. 2007 Oct 30;240(1-2):70-85.

[6]Geling Teng,et al. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro. Mol Med Rep. 2016 Dec;14(6):5164-5170.