Tirapazamine
Tirapazamine is an anticancer chemotherapeutic compound currently in clinical trials co-administered with cisplatin or radiation as a potential treatment for several cancers. Tirapazamine inhibits DNA topoisomerase IIα and modulates replication protein A (RPA), inhibiting DNA replication. Tirapazamine also forms DNA damaging free radicals, inducing single- and double-stranded DNA breaks. Additionally, tirapazamine inhibits expression of HIF-1α, potentially through modulation of eukaryotic initiation factor eIF2α phosphorylation. This compound induces apoptosis in neuroblastoma cells, decreasing the mitochondrial membrane potential and levels of glutathione; this effect may be p53-dependent.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18976564
| Cas No. |
27314-97-2 |
|---|---|
| Purity |
≥98% |
| Formula |
C7H6N4O2 |
| Formula Wt. |
178.15 |
| IUPAC Name |
4-hydroxy-1-oxido-1,2,4-benzotriazin-1-ium-3-imine |
| Synonym |
SR 4233 |
| Appearance |
Orange-red crystalline powder |
Zhang J, Cao J, Weng Q, et al. Suppression of hypoxia-inducible factor 1α (HIF-1α) by tirapazamine is dependent on eIF2α phosphorylation rather than the mTORC1/4E-BP1 pathway. PLoS One. 2010 Nov 9;5(11):e13910. PMID: 21085474.
Yang B, Reynolds CP. Tirapazamine cytotoxicity for neuroblastoma is p53 dependent. Clin Cancer Res. 2005 Apr 1;11(7):2774-80. PMID: 15814660.
Peters KB, Wang H, Brown JM, et al. Inhibition of DNA replication by tirapazamine. Cancer Res. 2001 Jul 15;61(14):5425-31. PMID: 11454687.
Brown JM, Wang LH. Tirapazamine: laboratory data relevant to clinical activity. Anticancer Drug Des. 1998 Sep;13(6):529-39. PMID: 9755717.
