| Identification | Back Directory | [Name]
3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE | [CAS]
27314-97-2 | [Synonyms]
TPZ
SR-4233
Tirazone
SR 259075
TIRAPAZAMINE
SR-4233, Tirapazamine
Tirapazamine(SR259075
SR-4233, Tirapazamine, TPZ
1,2,4-benzotriazin-3-amine,1,4-dioxide
3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE
1,2,4-benzotriazine,3-amino-,1,4-dioxide
4-Hydroxy-1-oxido-1,2,4-benzotriazin-1-ium-3-imine | [EINECS(EC#)]
636-678-5 | [Molecular Formula]
C7H6N4O2 | [MDL Number]
MFCD00132954 | [MOL File]
27314-97-2.mol | [Molecular Weight]
178.15 |
| Chemical Properties | Back Directory | [Appearance]
Orange Needles | [Melting point ]
220°C dec. | [Boiling point ]
493.6±28.0 °C(Predicted) | [density ]
1.68±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble10mg/mL, clear | [form ]
powder | [pka]
1.51±0.30(Predicted) | [color ]
orange to dark orange-red | [InChI]
InChI=1S/C7H6N4O2/c8-7-9-11(13)6-4-2-1-3-5(6)10(7)12/h1-4H,(H2,8,9) | [InChIKey]
ORYDPOVDJJZGHQ-UHFFFAOYSA-N | [SMILES]
[N+]1([O-])C2=CC=CC=C2[N+]([O-])=C(N)N=1 |
| Hazard Information | Back Directory | [Chemical Properties]
Orange Needles | [Uses]
A bioreductive anticancer agent. Selectively toxic to cells under hypoxic conditions. An antineoplastic | [Definition]
ChEBI: A member of the class of benzotriazines that is 1,2,4-benzotriazine carrying an amino substituent at position 3 and two oxido substituents at positions 1 and 4. | [Description]
Tirapazamine is a hypoxia-activated anticancer agent.1 It is converted to an oxidizing radical under hypoxic conditions and can induce single- and double-strand breaks in DNA, formation of trapped topoisomerase I- and II-DNA complexes, and other chromosomal aberrations, leading to cytotoxicity.1,2,3 Tirapazamine induces hypoxia-enhanced cytotoxicity in DT40 cells (IC50s = 1.02 and 4.34 μM in hypoxic and normoxic conditions, respectively).3 It also induces cytotoxicity in HT-1080 and A549 cells in a concentration-dependent manner under hypoxic conditions.1 In vivo, tirapazamine sensitizes tumors to cisplatin (Item No. 13119) in a mouse RIF-1 fibrosarcoma tumor model.4 Tirapazamine (0.08 mmol/kg) also sensitizes tumors to fractionated irradiation in a FaDu hypopharyngeal squamous cell carcinoma mouse xenograft model.5 | [Biochem/physiol Actions]
Under hypoxic conditions, tirapazamine is a potent cytotoxic agent that induces apoptosis by inducing breaks in single and double stranded DNA, as well as chromosomal breaks. The compound sensitizes cells to other ionizing radiation and other cytotoxic agents like cisplatin. | [References]
[1] BROWN J. SR 4233 (Tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours[J]. British Journal of Cancer, 1993, 67 6: 1163-1170. DOI: 10.1038/bjc.1993.220
[2] SRINI B REDDY Stephen K W. Tirapazamine: a novel agent targeting hypoxic tumor cells.[J]. Expert opinion on investigational drugs, 2009, 18 1: 77-87. DOI: 10.1517/13543780802567250
[3] TAKAHITO MORIWAKI. Cytotoxicity of Tirapazamine (3-Amino-1,2,4-benzotriazine-1,4-dioxide)-Induced DNA Damage in Chicken DT40 Cells[J]. Chemical Research in Toxicology, 2016, 30 2: 699-704. DOI: 10.1021/acs.chemrestox.6b00417
[4] M J DORIE J M B. Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin.[J]. Cancer research, 1993, 53 19: 4633-4636.
[5] A EL SAID. Comparison of the effectiveness of tirapazamine and carbogen with nicotinamide in enhancing the response of a human tumor xenograft to fractionated irradiation.[J]. Radiation oncology investigations, 1999, 7 3: 163-169. DOI: 10.1002/(sici)1520-6823(1999)7:3<163::aid-roi5>3.0.co;2-m |
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