[CAS NO. 252979-56-9] Banoxantronedihydrochloride
PRODUCTS SPECIFICATIONS [252979-56-9]
DESCRIPTION [252979-56-9]
Overview
| MDL | MFCD19690955 |
|---|---|
| Molecular Weight | 517.40 |
| Molecular Formula | C22H30Cl2N4O6 |
| SMILES | O=C1C2=C(C(O)=CC=C2O)C(C3=C(NCC[N+](C)(C)[O-])C=CC(NCC[N+](C)(C)[O-])=C13)=O.Cl.Cl |
2 Publications Citing Use of MCE
Summary
Banoxantrone dihydrochloride is a novel bioreductive agent that can be reduced to a stable, DNA-affinic compound AQ4, which is a potent topoisomerase II inhibitor.
IC50 & Target
|
Topoisomerase II |
In Vitro
Banoxantrone (AQ4N) can be reduced in a hypoxic environment to a stable DNA-affinic agent AQ4. AQ4, a potent topoisomerase II inhibitor, would be capable of damaging cells recruited into the cell cycle following radiation damage to the well-oxygenated cells of the tumor [1] . Banoxantrone shows more than 8-fold higher cytotoxicity under hypoxia than normoxia in cultures of 9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells but not for 11 other human cancer cell lines. DT-diaphorase protein levels and banoxantrone chemosensitivity are poorly correlated across the cancer cell line panel, and banoxantrone chemosensitivity is not affected by DT-diaphorase inhibitors [2] . Banoxantrone is a bis-N-oxide that is reduced via two sequential two-electron reductions to the tertiary amine, AQ4, which is a potent cytotoxic agent toward both aerobic and hypoxic cells. AQ4, but not AQ4N, intercalates in DNA with high affinity to generate a stable persistent complex that can inhibit topoisomerase II and cause DNA damage and cell death [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Banoxantrone (200 mg/kg) significantly enhances the tumor growth delay caused by radiation. This occurred when radiation is administered both as a single dose (12 Gy) and in a multifraction regimen (5x3 Gy). A study of the scheduling of Banoxantrone (AQ4N) administration shows that there is a very long time period over which a maximal effect can be elicited (drug given 4 days before to 6 h after radiation). These results suggest that Banoxantrone has significant potential as a bioreductive drug [1] . The activation of banoxantrone cytotoxicity in vivo requires tumor hypoxia that is more extensive or prolonged than can readily be achieved by vasodilation or by antiangiogenic drug treatment [2] . Incorporation of banoxantrone into conventional chemoradiation protocols therefore targets both oxygenated and hypoxic regions of tumors, and potentially will increase the effectiveness of therapy. A single dose of 60 mg/kg banoxantrone enhances the response of RT112 (bladder) and Calu-6 (lung) xenografts to treatment with cisplatin and radiation therapy. Banoxantrone will increase the efficacy of chemoradiotherapy in preclinical models [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
Solvent & Solubility
DMSO : 12.5 mg/mL ( 24.16 mM ; Need ultrasonic)
H 2 O : 9.52 mg/mL ( 18.40 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9327 mL | 9.6637 mL | 19.3274 mL |
| 5 mM | 0.3865 mL | 1.9327 mL | 3.8655 mL |
| 10 mM | 0.1933 mL | 0.9664 mL | 1.9327 mL |
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1.
Add each solvent one by one: PBS
Solubility: 8.33 mg/mL (16.10 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
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2.
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3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 7.5 mg/mL (14.50 mM); Clear solution
References
- [1] Hejmadi MV, et al. DNA damage following combination of radiation with the bioreductive drug AQ4N: possible selective toxicity to oxic and hypoxic tumour cells. Br J Cancer. 1996 Feb;73(4):499-505.
- [2] Manley E Jr, et al. Impact of tumor blood flow modulation on tumor sensitivity to the bioreductive drug banoxantrone. J Pharmacol Exp Ther. 2013 Feb;344(2):368-77.
- [3] Williams KJ, et al. In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenografts. Mol Cancer Ther. 2009 Dec;8(12):3266-75.
