Tirapazamine

Tirapazamine

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Systematic (IUPAC) name
4-hydroxy-1-oxido-1,2,4-benzotriazin-1-ium-3-imine
Identifiers
CAS Number	27314-97-2
ATC code	none
PubChem	CID 33776
Chemical data
Formula	C7H6N4O2
Molar mass	178.148 g/mol[[]]

Tirapazamine (SR-4233) is an experimental anticancer drug that is activated to a toxic radical only at very low levels of oxygen (hypoxia). Such levels are common in human solid tumors, a phenomenon known as tumor hypoxia. Thus, tirapazamine is activated to its toxic form preferentially in the hypoxic areas of solid tumors. Cells in these regions are resistant to killing by radiotherapy and most anticancer drugs. Thus the combination of tirapazamine with conventional anticancer treatments is particularly effective. As of 2006, tirapazamine is undergoing phase III testing in patients with head and neck cancer and gynecological cancer, and similar trials are being undertaken for other solid tumor types.

Chemically it is an aromatic heterocycle di-N-oxide. Its full chemical name is 3-amino-1,2,4-benzotriazine-1,4 dioxide. Originally it was prepared in a programme screening for new herbicides in 1972. Its clinical use was first described by Zeman et al. in 1986. While tirapazamine has had only limited effectiveness in clinical trials, it has been used as a lead compound to develop a number of newer compounds with improved anti-cancer properties.

An update of a Phase III trial (Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): a phase III trial of the Trans-Tasman Radiation Oncology Group) found no evidence that the addition of TPZ to chemoradiotherapy, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improved overall survival.

External links

• ClinicalTrials.gov NCT00033410 Chemotherapy, Tirapazamine, and Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancerfr:Tirapazamine

Denny, WA (2004). "Prospects for hypoxia-activated anticancer drugs". Current medicinal chemistry. Anti-cancer agents. 4 (5): 395–9. doi:10.2174/1568011043352812. PMID 15379691. 

Gandara, DR; Lara Jr, PN; Goldberg, Z; Le, QT; Mack, PC; Lau, DH; Gumerlock, PH (2002). "Tirapazamine: prototype for a novel class of therapeutic agents targeting tumor hypoxia". Seminars in oncology. 29 (1 Suppl 4): 102–9. doi:10.1053/sonc.2002.31531. PMID 11894020. 

Zeman, EM; Brown, JM; Lemmon, MJ; Hirst, VK; Lee, WW (1986). "SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells". International journal of radiation oncology, biology, physics. 12 (7): 1239–42. PMID 3744945. 

Rischin, D; Peters, LJ; O'Sullivan, B; Giralt, J; Fisher, R; Yuen, K; Trotti, A; Bernier, J; Bourhis, J (2010). "Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): a phase III trial of the Trans-Tasman Radiation Oncology Group". Journal of clinical oncology. 28 (18): 2989–95. doi:10.1200/JCO.2009.27.4449. PMID 20479425.