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Tirapazamine

替拉扎明
Catalog No.
B3399
抗癌药
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 454.00
现货
50mg
¥ 545.00
现货
200mg
¥ 1,609.00
现货

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A

背景

IC50:N/A

Tirapazamine(SR259075\Win59075和SR4233)是实验抗癌药,仅在氧水平极低时可活化为毒性自由基,该现象称作肿瘤缺氧.

体外:Tirapazamine通过减少HIF-1α蛋白合成,可下调HIF-1α表达.Tirapazamine加SN-38(irinotecan的活化代谢物)可诱导细胞凋亡增加,并出现线粒体去极化增加和caspase通路激活[1].

体内:Tirapazamine加SN-38疗法可显著阻断HIF-1α蛋白积累,降低HIF-1α转录活化,并可减弱同源重组修复途径中蛋白的磷酸化,最终导致两种药物的协同作用.而且,tirapazamine与irinotecan联合使用可增加抗癌效果,在人类肝癌Bel-7402异种移植小鼠模型中扮演进一步的作用[1].大鼠腹腔内注射两种剂量[5(5TP)和10 mg(10TP)]的tirapazamine六次,每周一次,而doxorubicin给药剂量为1.8 mg(DOX).随后两组同时接受两种药物(5TP+DOX和10TP+DOX).Tirapazamine可降低心脏脂质过氧化,doxorubicin可以使RyR2蛋白提高至正常水平[2].

临床试验:临床试验已进行.

参考文献:
[1].  Cai TY1, Liu XW, Zhu H, Cao J, Zhang J, Ding L, Lou JS, He QJ, Yang B. Tirapazamine sensitizes hepatocellular carcinoma cells to topoisomerase I inhibitors via cooperative modulation of hypoxia-inducible factor-1α. Mol Cancer Ther. 2014 Mar;13(3):630-42.
[2].  Sliwinska J1, Dudka J, Korga A, Burdan F, Matysiak W, Jodlowska-Jedrych B, Mandziuk S, Dawidek-Pietryka K.Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca balance protein levels. Oxid Med Cell Longev. 2012;2012:890826.

文献引用

化学属性

Physical AppearanceA solid
StorageStore at -20°C
M.Wt178.15
Cas No.27314-97-2
FormulaC7H6N4O2
Solubilityinsoluble in H2O; insoluble in EtOH; ≥8.9 mg/mL in DMSO
Chemical Name4-hydroxy-1-oxido-1,2,4-benzotriazin-1-ium-3-imine
SDFDownload SDF
Canonical SMILESC1=CC=C2C(=C1)N(C(=N)N=[N+]2[O-])O
运输条件 蓝冰运输或根据您的需求运输。
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试验操作

Cell experiment:[1]

Cell lines

Human liver cancer Bel-7402 cells

Reaction Conditions

0 ~ 10 μM tirapazamine

Applications

Tirapazamine dose-dependently inhibited the transcriptional activity (0 ~ 10 μM; 6 h) and the protein level (0 ~ 10 μM; 12 h) of HIF-1α under hypoxia. Moreover, tirapazamine (0 ~ 5 μM; 24 h) enhanced the cytotoxicity elicited by topoisomerase I inhibitors (i.e. SN-38, TPT, HCPT and MONCPT) under hypoxic conditions.

Animal experiment:[1]

Animal models

5- to 6-week-old BALB/c male athymic mice xenografted with Bel-7402 cells

Dosage form

25 mg/kg

Administered by intraperitoneal injection every 2 days for 27 days

Applications

The combination of tirapazamine and irinotecan caused marked tumor growth inhibition that was significantly greater than that caused by tirapazamine or irinotecan treatment alone. Furthermore, compared with the initial body weights, the mice treated with the combination showed no significant body weight loss on day 26.

Note

The technical data provided above is for reference only.

References:

1. Cai TY, Liu XW, Zhu H, et al. Tirapazamine sensitizes hepatocellular carcinoma cells to topoisomerase I inhibitors via cooperative modulation of hypoxia-inducible factor-1α. Molecular Cancer Therapeutics, 2014, 13(3): 630-642.

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