Tirapazamine
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.
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.
| 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 |
| SDF | Download SDF |
| Canonical SMILES | C1=CC=C2C(=C1)N(C(=N)N=[N+]2[O-])O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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. |
|
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
