Tirapazamine

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Tirapazamine

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

27314-97-2

包装与价格：

包装	价格(元)
10mM (in 1mL DMSO)	电议
50mg	电议
200mg	电议

产品介绍

化学性质

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	178.15
Cas No.	27314-97-2
Formula	C₇H₆N₄O₂
Solubility	insoluble in H2O; insoluble in EtOH; ≥8.9 mg/mL in DMSO
Chemical Name	4-hydroxy-1-oxido-1,2,4-benzotriazin-1-ium-3-imine
Canonical SMILES	C1=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。
一般建议	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。

资料参考

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.

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.