Tirapazamine
Tirapazamine (CAS 27314-97-2), also known as SR259075, Win59075, or SR4233, is an investigational anticancer agent selectively activated under hypoxic conditions characteristic of solid tumors. The compound is bioreduced in hypoxic tumor microenvironments to cytotoxic free radicals, leading to cellular damage. Tirapazamine downregulates hypoxia-inducible factor-1α (HIF-1α), thereby influencing pathways associated with tumor adaptive mechanisms to hypoxia. Combined treatment with tirapazamine and topoisomerase I inhibitors (such as SN-38, the active metabolite of irinotecan) enhances apoptosis via mitochondria-mediated caspase activation and weakened DNA repair signaling. Preclinical investigations, including hepatocellular carcinoma xenografts, confirm this enhanced tumor suppression. Clinical trials evaluating tirapazamine's anticancer efficacy are ongoing.
| 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] | |
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Cell lines |
Human liver cancer Bel-7402 cells |
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Reaction Conditions |
0 ~ 10 μM tirapazamine |
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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] | |
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Animal models |
5- to 6-week-old BALB/c male athymic mice xenografted with Bel-7402 cells |
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Dosage form |
25 mg/kg Administered by intraperitoneal injection every 2 days for 27 days |
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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. |
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Note |
The technical data provided above is for reference only. |
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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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