chemistry

Tirapazamine

Tirapazamine is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Tirapazamine rather than just read about it. In short: Tirapazamine (SR-4233, WIN 59075) 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.

Key takeaways

Tirapazamine belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Tirapazamine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Tirapazamine from memory before moving on to harder problems.

Reference excerpt

Tirapazamine (SR-4233, WIN 59075) 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 program 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. Two possible molecular mechanisms of TPZ, for generating reactive oxygen species which causes DNA strand break, have been considered widely. In hypoxia, under bioreductive condition, it has been observed that TPZ primarily produces hydroxyl or and benzotriazinyl radicals as the DNA damaging reactive species. A new clinical phase I trial of Tirapazamine combined with embolization in liver cancer has been received in June, 2014. This study will help to optimize the safe tolerable dose of TPZ, when it is administered with embolization in liver cancer. Treatment of solid tumors is complicated by the fact that these are often poorly provided with blood vessels, thus limiting their exposure to cytotoxic agents. Attempts have, however, been made to take advantage of the resulting hypoxic environment by designing drugs that are nonreactive until they are reduced to reactive species in oxygen-deficient tissues. This, it is hoped, will lead to enhanced selectivity. The azaquinoxaline dioxide function on the antineoplastic agent tirapazamine, for example, has been shown to give reactive nitroxide radicals on reduction.

Synthesis

The condensation of 2-nitroaniline [88-74-4] (1) with cyanamide [420-04-2] (2) probably initially involves the formation of guanidinonitrobenzene [70973-04-5] (3). The very basic nitrogen in that species then condenses with the adjacent nitro group, closing the ring to give 1,2,4-Benzotriazin-3-amine 1-oxide [5424-06-6] (4). Oxidation with hydrogen peroxide then completes the preparation of tirapazamine (5).

References

External links Clinical trial number NCT00033410 for "Chemotherapy, Tirapazamine, and Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer" at ClinicalTrials.gov

Illustrations

Worked examples

Example 1 — a first encounter with Tirapazamine

Start with the simplest possible case. Write down what Tirapazamine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Tirapazamine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Tirapazamine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Tirapazamine

In research: Tirapazamine appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Tirapazamine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Tirapazamine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Amine oxides, Benzotriazines, Drugs not assigned an ATC code, so understanding it makes those chapters shorter.
In everyday life: Look for Tirapazamine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Tirapazamine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Tirapazamine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Tirapazamine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Tirapazamine in simple terms?

Why does Tirapazamine matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Tirapazamine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Tirapazamine.