| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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Banoxantrone 2HCl (AQ4N), the dihydrochloride salt of Banoxantrone, is a hypoxia-activated and bioreductive prodrug that can be reduced under hypoxia (e.g. in hypoxic cells) to a stable, compound AQ4, which is a potent topoisomerase II inhibitor with antitumor activity.
| Targets |
Topoisomerase II
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|---|---|
| ln Vitro |
Banoxantrone (AQ4N) can be reduced to the stable DNA-affinic agent AQ4 in a hypoxic environment. Potent topoisomerase II inhibitor AQ4 can harm cells that are recruited into the cell cycle after radiation damages the tumor's well-oxygenated cells[1]. In cultures of 9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells, benoxantrone exhibits more than 8-fold higher cytotoxicity under hypoxia than normoxia, but not for 11 other human cancer cell lines. Banoxantrone chemosensitivity and DT-diaphorase protein levels have weak correlations across the panel of cancer cell lines, and DT-diaphorase inhibitors have no effect on banoxantrone chemosensitivity[2]. Banoxantrone is a bis-N-oxide that undergoes two consecutive two-electron reductions to produce AQ4, a tertiary amine that is highly cytotoxic to both aerobic and hypoxic cells. A stable, long-lasting complex that can inhibit topoisomerase II, damage DNA, and kill cells is produced when AQ4, but not AQ4N, intercalates in DNA with high affinity[3].
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| ln Vivo |
Banoxantrone (200 mg/kg) considerably amplifies the radiation-induced tumor growth delay. This happens when radiation is given in a multifraction regimen (5x3 Gy) as well as a single dose (12 Gy). A review of the best times to administer banoxantrone (AQ4N) reveals that there is a very long window of time during which the drug's maximum effects can be produced (drug given 4 days before to 6 h after radiation). These findings imply that benoxantrone has a great deal of promise as a bioreductive medication[1]. Tumor hypoxia that is more profound or prolonged than what is easily accomplished by vasodilation or antiangiogenic medication therapy is necessary for the activation of banoxantrone cytotoxicity in vivo[2]. Therefore, banoxantrone targets both oxygenated and hypoxic regions of tumors and may increase therapy effectiveness when added to standard chemoradiation protocols. The response of RT112 (bladder) and Calu-6 (lung) xenografts to cisplatin and radiation therapy is improved by a single dose of 60 mg/kg banoxantrone. In preclinical models, bainostantrone will boost the effectiveness of chemoradiotherapy[3].
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| Enzyme Assay |
Tumors T50/80 that have not received treatment and have a geometric diameter (GMD) of 6.5–9.0 mm are removed and then mechanically broken up in ice-cold phosphate-buffered saline (PBS). Filtration through a 40μm mesh screen is used to create single cell suspensions. After centrifugation, these are resuspended at a density of 106 cells/mL in Eagle's minimal essential medium (EMEM) supplemented with 10% fetal calf serum (FCS). Glass bottles with rubber seals, capacity 125 mL, are filled with cells (20 mL). In order to create well-oxygenated conditions, such as 95% air/5% carbon dioxide, or hypoxic conditions, such as 95% N2/5% CO2, these are gassed for two hours at 37°C. During the final ninety minutes of this duration, benoxintrone (AQ4N) (20μM) is injected via the sealed lid. Cells are resuspended in fresh medium after the drug has been removed. Aliquots (105 cells) are processed at different times after this procedure, ranging from 0 to 96 hours, for the purpose of analyzing DNA damage. Samples are also kept in the culture medium above for 24 hours at 37°C, 95% air/5% CO2 in order to assess the impact of keeping the removed tumor cells in culture. After the cells are harvested and put in glass bottles, the experiment described above is conducted. The cells grow in suspension. Every experiment is run twice, with the results combined[1].
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| Animal Protocol |
Mice: Tumor-bearing T50/80 mice are employed. When tumors reach a geometric diameter (GMD) of 6.5–9.0 mm, these experiments are conducted. One intraperitoneal injection (i.p.) of benoxantrone (AQ4N) at a dose of 200 mg/kg is given. The medication is administered half an hour prior to a single 12 Gy dose of X-ray radiation (300 kVp Siemens Stabilipan at a dose rate of 2.56 Gy min-1). After treatment, tumors are removed at various intervals and put on ice. As mentioned above, single cell suspensions are made in ice-cold PBS. The cells are diluted in cold EMEM containing 10% FCS (1x106 cells/mL) after centrifugation. For the comet assay, an aliquot containing 100 μL of this suspension is utilized. Tumors removed at different times intervals from 0 to 120 hours after irradiation undergo this process. The findings from three different experiments are combined.
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| References |
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| Molecular Formula |
C₂₂H₃₀CL₂N₄O₆
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|---|---|
| Molecular Weight |
517.402803897858
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| Exact Mass |
516.154
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| Elemental Analysis |
C, 51.07; H, 5.84; Cl, 13.70; N, 10.83; O, 18.55
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| CAS # |
252979-56-9
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| Related CAS # |
136470-65-0 (Free base); 70476-63-0 (AQ4); 252979-56-9 (2HCl)
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| PubChem CID |
72941779
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| Appearance |
Blue to dark blue solid powder
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| LogP |
3.637
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
644
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.[O-][N+](C)(C)CCNC1C=CC(=C2C(C3C(=CC=C(C=3C(C2=1)=O)O)O)=O)NCC[N+](C)(C)[O-]
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| InChi Key |
SBWCPHUXRZRTDP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H28N4O6.2ClH/c1-25(2,31)11-9-23-13-5-6-14(24-10-12-26(3,4)32)18-17(13)21(29)19-15(27)7-8-16(28)20(19)22(18)30;;/h5-8,23-24,27-28H,9-12H2,1-4H3;2*1H
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| Chemical Name |
2-[[4-[2-[dimethyl(oxido)azaniumyl]ethylamino]-5,8-dihydroxy-9,10-dioxoanthracen-1-yl]amino]-N,N-dimethylethanamine oxide;dihydrochloride
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| Synonyms |
AQ-4N; AZD-1689; AQ4N; AZD1689; AQ 4N; AZD 1689
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~25 mg/mL (~48.3 mM)
H2O: ~20 mg/mL (~38.7 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (14.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 7.5 mg/mL (14.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 8.33 mg/mL (16.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00109356 | Unknown | Drug: AQ4N (Chemotherapy) |
Non-Hodgkin's Lymphoma Small Lymphocytic Leukemia |
Novacea | March 2005 | Phase 1 Phase 2 |
| NCT00394628 | Unknown | Drug: AQ4N Drug: Temozolomide |
Glioblastoma Multiforme | Novacea | October 2006 | Phase 1 Phase 2 |
| NCT00090727 | Unknown | Drug: AQ4N | Solid Malignancies Non-Hodgkin's Lymphoma |
Novacea | August 2004 | Phase 1 |
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