Tirapazamine

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Tirapazamine, also known as SR-4233 or WIN 59075, is an experimental anticancer drug. It is designed to become toxic mainly in very low-oxygen conditions, called hypoxia, which are common in solid tumors. Because hypoxic tumor areas are often resistant to radiation and many drugs, tirapazamine can help target cancer cells that are hard to kill with standard treatments.

In the lab and in early trials, tirapazamine works by producing DNA-damaging radicals when it is reduced in hypoxic cells. This makes it a good partner for conventional cancer therapies, since it can attack tumor cells that other treatments miss.

As of 2006, tirapazamine was in phase III testing for head and neck cancer and gynecological cancers, with other solid tumors also studied. A major phase III trial added tirapazamine to cisplatin and radiation for advanced head and neck cancer not chosen for hypoxia, but it did not show an overall survival benefit.

Chemically, tirapazamine is an aromatic heterocycle di-N-oxide with the full name 3-amino-1,2,4-benzotriazine-1,4-dioxide. It was first prepared in 1972 during herbicide screening, and its clinical use was described in 1986. It has inspired the development of newer anticancer drugs. There has also been early work, including a 2014 phase I study, on using tirapazamine with liver tumor embolization to find safe dosing.