Banoxantrone
Identification
- Generic Name
- Banoxantrone
- DrugBank Accession Number
- DB04975
- Background
Banoxantrone is a highly selective bioreductive drug that is activated in, and is preferentially toxic to, hypoxic cells in tumours. It has been shown to work synergistically with fractionated radiation to significantly delay growth of tumours compared to administration of either banoxantrone or radiation alone. Banoxantrone was also efficacious in tumour models when administered in combination with either cisplatin or chemoradiation. 5
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 444.488
Monoisotopic: 444.200884638 - Chemical Formula
- C22H28N4O6
- Synonyms
- Banoxantrone
- External IDs
- AQ 4N
- AQ4N
Pharmacology
- Indication
For the treatment of various forms of cancer.
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- Pharmacodynamics
AQ4N was rationally designed to have anti-tumor activity following bioreduction by tissue cytochrome P450 to AQ4, an active DNA topoisomerase II inhibitor. Preclinical studies demonstrated AQ4N selectively targets lymphoid tissues and hypoxic tumor tissues.
- Mechanism of action
Banoxantrone (formally known as AQ4N) is preferentially and irreversibly converted to AQ4, its cytotoxic form, in hypoxic tumour cells where it remains localised. When the surrounding oxygenated cells are killed by radiotherapy or chemotherapy bringing these AQ4-containing quiescent cells closer to the oxygen source, they become reoxygenated, attempt to resume replication and, in this state, are killed by AQ4 through potent DNA intercalation and topoisomerase II inhibition.
Target Actions Organism UDNA topoisomerase 2-alpha Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
AQ4N is selectively and irreversibly converted to AQ4, its cytotoxic form, in hypoxic tumor cells, which are its targeted site of action.
- Route of elimination
Not Available
- Half-life
0.64 to 0.83 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Banoxantrone can be increased when it is combined with Abametapir. Abatacept The metabolism of Banoxantrone can be increased when combined with Abatacept. Adalimumab The metabolism of Banoxantrone can be increased when combined with Adalimumab. Alpelisib The metabolism of Banoxantrone can be increased when combined with Alpelisib. Ambroxol The risk or severity of methemoglobinemia can be increased when Banoxantrone is combined with Ambroxol. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as anthraquinones. These are organic compounds containing either anthracene-9,10-quinone, 1,4-anthraquinone, or 1,2-anthraquinone.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Anthracenes
- Sub Class
- Anthraquinones
- Direct Parent
- Anthraquinones
- Alternative Parents
- Aryl ketones / Secondary alkylarylamines / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous amides / Vinylogous acids / Trialkyl amine oxides / Trisubstituted amine oxides and derivatives / Organic zwitterions / Organic salts / Organic oxides show 1 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 9,10-anthraquinone / Amine / Anthraquinone / Aromatic homopolycyclic compound / Aryl ketone / Hydrocarbon derivative / Ketone / N-oxide / Organic nitrogen compound show 13 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- W5H7E45YT3
- CAS number
- 136470-65-0
- InChI Key
- YZBAXVICWUUHGG-UHFFFAOYSA-N
- InChI
- 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
- IUPAC Name
- 2-[(4-{[2-(dimethyl-oxo-$l^{5}-azanyl)ethyl]amino}-5,8-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]-N,N-dimethylethanamine oxide
- SMILES
- C[N+](C)([O-])CCNC1=CC=C(NCC[N+](C)(C)[O-])C2=C1C(=O)C1=C(O)C=CC(O)=C1C2=O
References
- General References
- McKeown SR, Cowen RL, Williams KJ: Bioreductive drugs: from concept to clinic. Clin Oncol (R Coll Radiol). 2007 Aug;19(6):427-42. Epub 2007 May 4. [Article]
- McErlane V, Yakkundi A, McCarthy HO, Hughes CM, Patterson LH, Hirst DG, Robson T, McKeown SR: A cytochrome P450 2B6 meditated gene therapy strategy to enhance the effects of radiation or cyclophosphamide when combined with the bioreductive drug AQ4N. J Gene Med. 2005 Jul;7(7):851-9. [Article]
- Atkinson SJ, Loadman PM, Sutton C, Patterson LH, Clench MR: Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom. 2007;21(7):1271-6. [Article]
- Lalani AS, Alters SE, Wong A, Albertella MR, Cleland JL, Henner WD: Selective tumor targeting by the hypoxia-activated prodrug AQ4N blocks tumor growth and metastasis in preclinical models of pancreatic cancer. Clin Cancer Res. 2007 Apr 1;13(7):2216-25. [Article]
- Patterson LH, McKeown SR, Ruparelia K, Double JA, Bibby MC, Cole S, Stratford IJ: Enhancement of chemotherapy and radiotherapy of murine tumours by AQ4N, a bioreductively activated anti-tumour agent. Br J Cancer. 2000 Jun;82(12):1984-90. [Article]
- Loadman PM, Swaine DJ, Bibby MC, Welham KJ, Patterson LH: A preclinical pharmacokinetic study of the bioreductive drug AQ4N. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):422-6. [Article]
- External Links
- PubChem Compound
- 9955116
- PubChem Substance
- 347827701
- ChemSpider
- 8130726
- ChEMBL
- CHEMBL117391
- ZINC
- ZINC000003776950
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0151 mg/mL ALOGPS logP 0.26 ALOGPS logP 1.65 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 8.45 Chemaxon pKa (Strongest Basic) 4.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 144.78 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 125.63 m3·mol-1 Chemaxon Polarizability 46.66 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-01q9-4029000000-36497f985574746dbdcc Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.99123 predictedDeepCCS 1.0 (2019) [M+H]+ 187.3868 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.39536 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ubiquitin binding
- Specific Function
- Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
- Gene Name
- TOP2A
- Uniprot ID
- P11388
- Uniprot Name
- DNA topoisomerase 2-alpha
- Molecular Weight
- 174383.88 Da
References
- Atkinson SJ, Loadman PM, Sutton C, Patterson LH, Clench MR: Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom. 2007;21(7):1271-6. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Yakkundi A, McErlane V, Murray M, McCarthy HO, Ward C, Hughes CM, Patterson LH, Hirst DG, McKeown SR, Robson T: Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N. Cancer Gene Ther. 2006 Jun;13(6):598-605. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- McCarthy HO, Yakkundi A, McErlane V, Hughes CM, Keilty G, Murray M, Patterson LH, Hirst DG, McKeown SR, Robson T: Bioreductive GDEPT using cytochrome P450 3A4 in combination with AQ4N. Cancer Gene Ther. 2003 Jan;10(1):40-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Yakkundi A, McErlane V, Murray M, McCarthy HO, Ward C, Hughes CM, Patterson LH, Hirst DG, McKeown SR, Robson T: Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N. Cancer Gene Ther. 2006 Jun;13(6):598-605. [Article]
- McErlane V, Yakkundi A, McCarthy HO, Hughes CM, Patterson LH, Hirst DG, Robson T, McKeown SR: A cytochrome P450 2B6 meditated gene therapy strategy to enhance the effects of radiation or cyclophosphamide when combined with the bioreductive drug AQ4N. J Gene Med. 2005 Jul;7(7):851-9. [Article]
Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51