| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
Banoxantrone (AQ4N) is a novel and potent bio-reductive prodrug that can be reduced under hypoxic conditions (hypoxia-activated) to a stable, DNA-affinic compound AQ4 (CAS#: 70476-63-0), which is a potent topoisomerase II inhibitor with anticanceractivity. Banoxantrone intercalates into and crosslinks DNA, and inhibits topoisomerase II. This results in an inhibition of DNA replication and repair in tumor cells. Combined with conventional therapeutic agents, both oxygenic and hypoxic regions of tumors can be targeted.
| Targets |
DNA intercalation; topoisomerase II
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|---|---|
| ln Vitro |
Tumor radiofrequency caused by benoxintrone (20 μM; 90 min) results in hypoxic T50/80 cell destruction [1].
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| ln Vivo |
Banoxantrone (200 mg/kg; intraperitoneal injection; single dosage) causes cell damage in BDF mice and greatly suppresses T50/80 tumors [1].
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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 10 6 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 (10 5 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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| Cell Assay |
Human tumor cells (HT29, WiDr, A549) were cultured in RPMI 1640. Hypoxic cells were pre-incubated in 1% O2 for 24 hours, then treated with Banoxantrone dihydrochloride (AQ4N) (0.1-100 μM, 4 hours) ± radiation. Clonogenic survival and DNA damage (alkaline elution/comet assay) were assessed. [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 (1x10 6 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.
Nude mice (6-8 weeks, female) were implanted with HT29/A549 cells. When tumors reached 100-150 mm³, Banoxantrone dihydrochloride (AQ4N) (100-200 mg/kg, IV in saline) was given, followed by radiation (1 Gy/min). Tumor volume was measured every 2-3 days; tissues were collected for histopathology/DNA damage analysis. [1]
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
AQ4N is selectively and irreversibly converted into its cytotoxic form, AQ4, in hypoxic tumor cells, which are its target sites. Biological Half-Life 0.64 to 0.83 hours |
| Toxicity/Toxicokinetics |
In nude mice (up to 200 mg/kg IV Banoxantrone dihydrochloride (AQ4N)), no significant changes in body weight, hematology, or liver/kidney function were observed. Histopathology showed no overt toxicity in normal tissues.
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| References |
[1]. 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]. Radiation enhances the therapeutic effect of Banoxantrone in hypoxic tumour cells with elevated levels of nitric oxide synthase. Oncol Rep. 2016 Apr;35(4):1925-32. |
| Additional Infomation |
Banoxantrone is a highly selective bioreducing drug that activates within hypoxic cells of tumors and preferentially exerts its toxic effects. Studies have shown that Banoxantrone synergistically delays tumor growth with fractionated radiotherapy compared to Banoxantrone alone or radiotherapy. In tumor models, Banoxantrone also demonstrates efficacy when used in combination with cisplatin or chemoradiotherapy. Banoxantrone is a bioreducing alkylaminoanthraquinone prodrug with antitumor activity. Under the hypoxic conditions common in solid tumors, Banoxantrone (AQ4N) is activated by cytochrome P450 enzymes highly expressed in certain tumors, generating the cytotoxic DNA binder AQ4. Banoxantrone can intercalate into and cross-link DNA while inhibiting topoisomerase II. This leads to suppression of DNA replication and repair in tumor cells. When used in combination with conventional therapies, it can target both oxygen-rich and hypoxic regions of the tumor. Drug Indications: For the treatment of various cancers. Mechanism of Action Banoxantrone (formerly AQ4N) is preferentially and irreversibly converted to its cytotoxic form, AQ4, in hypoxic tumor cells, where it remains. When surrounding oxygen-rich cells are killed by radiotherapy or chemotherapy, bringing these AQ4-containing quiescent cells closer to an oxygen source, they regain oxygen, attempt to resume replication, and are killed by AQ4 in this state through potent DNA intercalation and topoisomerase II inhibition. Pharmacodynamics AQ4N is designed to exert its antitumor activity after being bioreduced to AQ4 (an active DNA topoisomerase II inhibitor) by tissue cytochrome P450. Preclinical studies have shown that AQ4N selectively targets lymphoid tissue and hypoxic tumor tissue.
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| Molecular Formula |
C22H28N4O6
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|---|---|
| Molecular Weight |
444.48092
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| Exact Mass |
444.201
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| Elemental Analysis |
C, 59.45; H, 6.35; N, 12.60; O, 21.60
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| CAS # |
136470-65-0
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| Related CAS # |
Banoxantrone dihydrochloride;252979-56-9;Banoxantrone-d12 dihydrochloride;1562066-98-1;Banoxantrone-d12;1562067-05-3
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| PubChem CID |
9955116
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.033
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
644
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[N+](C)(CCNC1=C2C(=C(C=C1)NCC[N+](C)(C)[O-])C(=O)C3=C(C=CC(=C3C2=O)O)O)[O-]
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| InChi Key |
YZBAXVICWUUHGG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H28N4O6/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
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| Chemical Name |
2,2'-(5,8-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azanediyl)bis(N,N-dimethylethanamine oxide)
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2498 mL | 11.2491 mL | 22.4982 mL | |
| 5 mM | 0.4500 mL | 2.2498 mL | 4.4996 mL | |
| 10 mM | 0.2250 mL | 1.1249 mL | 2.2498 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.
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