Tirapazamine
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Overview
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.
References
- Denny WA (2004). "Prospects for hypoxia-activated anticancer drugs". Curr Med Chem Anti-Canc Agents 4 (5): 395-9. PMID 15379691.
- Gandara DR, Lara PN Jr, Goldberg Z, Le QT, Mack PC, Lau DH, Gumerlock PH (2002). "Tirapazamine: prototype for a novel class of therapeutic agents targeting tumor hypoxia". Semin Oncol 29 (1 Suppl 4): 102-9. 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". Int J Radiat Oncol Biol Phys 12 (7): 1239-42. PMID 3744945.
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
