| Stereochemistry | ACHIRAL |
| Molecular Formula | C7H6N4O2 |
| Molecular Weight | 178.1481 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=N[N+]([O-])=C2C=CC=CC2=[N+]1[O-]
InChI
InChIKey=ORYDPOVDJJZGHQ-UHFFFAOYSA-N
InChI=1S/C7H6N4O2/c8-7-9-11(13)6-4-2-1-3-5(6)10(7)12/h1-4H,(H2,8,9)
| Molecular Formula | C7H6N4O2 |
| Molecular Weight | 178.1481 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Tumor hypoxia remains one of the greatest challenges in the treatment of solid tumors, as cancer cells in these regions are resistant to killing by radiation therapy and most anticancer drugs. Tirapazamine (3-Amino-1,2,4-benzotriazine-1,4-dioxide or SR 4233) is a cytotoxic drug with selective toxicity towards hypoxic mammalian cells. Under both aerobic and hypoxic conditions, tirapazamine is reduced by an intracellular reductase to form a highly reactive radical, which can cause DNA single- and double-strand breaks. In addition, tirapazamine under hypoxic conditions reduces the activity of topoisomerase II and stabilizes DNA topoisomerase II cleavable complexes, and these complexes remain bound to DNA. Despite the very promising results obtained in various preclinical studies and early-Phase clinical trials, several Phase III trials have failed to demonstrate any survival benefit of adding tirapazamine to chemotherapy or radiation therapy of cancers.
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Eligible women for this study were those with a diagnosis of locally advanced cervix cancer, who were less than 75 years of age, having provided informed consent, and who had undergone the necessary prestudy investigations. External-beam radiotherapy (RT) was given to a minimum dose of 4500 cGy in 25 fractions (Day 1-35), and brachytherapy then delivered to bring the total dose at point A to 8500 cGy. The first dose level of the study used tirapazamine (TPZ) 190 mg/m(2) and cisplatin 75 mg/m(2) on Days 1, 15, and 29 of RT. TPZ 160 mg/m(2) alone was used on Days 8, 10, 12 and 22, 24, 26 of RT. A conventional dose-escalation step method was then used to determine the maximum tolerated dose (MTD) of TPZ.
Route of Administration:
Intravenous
Tirapazamine-treated V79 Chinese hamster cells were tested for cytotoxicity by colony assay and growth inhibition by the MTT assay. The survival of V79 cells after being exposed to 100 microM of tirapazamine for 2 h was about 78% of untreated controls. The mitotic cell counts of V79 cells approached zero after 4 h treatment of tirapazamine at 100 microM or 3 h at 300 microM. The fragmentation pattern of DNA isolated from cells 2 h after 300 microM tirapazamine treatment showed characteristics of apoptotic cells.
