Tirapazamine
(Synonyms: 替拉扎明; SR259075; SR4233; Win59075; SML 0552; SR 259075; Tirazone) 目录号 : GC11150
A hypoxia-activated anticancer agent
Cas No.:27314-97-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
IC50: N/A
Tirapazamine (SR259075; Win59075; SR4233) is an experimental anticancer drug that is activated to a toxic radical only at very low levels of oxygen; a phenomenon known as tumor hypoxia.
In vitro: Tirapazamine could downregulate HIF-1α expression by reducing HIF-1α protein synthesis. The enhanced apoptosis induced by tirapazamine plus SN-38 (the active metabolite of irinotecan) was followed by increased mitochondrial depolarization and caspase pathway activation [1].
In vivo: Tirapazamine plus SN-38 treatment dramatically blocked the accumulation of HIF-1α protein, reduced the HIF-1α transcriptional activation, and weakened the phosphorylation of proteins in the homologous recombination repair pathway, ultimately resulting in the synergism of these two drugs. Moreover, the increased anticancer efficacy of tirapazamine combined with irinotecan played a further role on a human liver cancer Bel-7402 xenograft mouse model [1]. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses [5 (5TP) and 10 mg (10TP)], while doxorubicin was administered in dose 1.8 mg (DOX). Subsequent two groups received both drugs at the same time (5TP+DOX and 10TP+DOX). Tirapazamine decreased heart lipid peroxidation and RyR2 protein was up to normal level altered by doxorubicin [2].
Clinical trial: Clinical study has been conducted.
IC50: N/A
替拉帕替汀（SR259075；Win59075；SR4233）是一种实验性抗癌药物，只在极低氧气水平下活化为有毒自由基，这种现象被称为肿瘤低氧。
体外研究：替拉帕替汀可通过减少HIF-1α蛋白质合成来下调HIF-1α表达。与SN-38（伊立替康的活性代谢物）联合应用的替拉帕替汀可增强细胞凋亡，同时还会导致线粒体去极化和caspase途径激活[1]。
体内研究：替拉帕替汀与SN-38联合治疗显著阻止了HIF-1α蛋白的积累，降低了HIF-1α转录激活，并减弱了同源重组修复途径中蛋白质的磷酸化，最终导致这两种药物的协同作用。此外，替拉帕替汀与伊立替康联合治疗还对人肝癌Bel-7402移植瘤小鼠模型的抗癌效果增强[1]。大鼠经腹腔注射替拉帕替汀（5TP和10TP两种剂量）六次，每周一次，同时给予多柔比星（DOX）1.8mg。接下来两组同时给予这两种药物（5TP+DOX和10TP+DOX）。替拉帕替汀降低了心脏的脂质过氧化，DOX引起的RyR2蛋白质也恢复到正常水平[2]。
临床试验：已进行了临床研究。
References:
[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.
| Cas No. | 27314-97-2 | SDF | |
| 别名 | 替拉扎明; SR259075; SR4233; Win59075; SML 0552; SR 259075; Tirazone | ||
| 化学名 | 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 | ||
| 分子式 | C7H6N4O2 | 分子量 | 178.15 |
| 溶解度 | ≥ 8.9mg/mL in DMSO | 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 | 5.6132 mL | 28.0662 mL | 56.1325 mL |
| 5 mM | 1.1226 mL | 5.6132 mL | 11.2265 mL |
| 10 mM | 0.5613 mL | 2.8066 mL | 5.6132 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。