Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H19N5O2.2C4H4O4 |
Molecular Weight | 557.5094 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 2 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.NCCNC1=CC=C(NCCN)C2=C1C(=O)C3=C(C=NC=C3)C2=O
InChI
InChIKey=SVAGFBGXEWPNJC-SPIKMXEPSA-N
InChI=1S/C17H19N5O2.2C4H4O4/c18-4-7-21-12-1-2-13(22-8-5-19)15-14(12)16(23)10-3-6-20-9-11(10)17(15)24;2*5-3(6)1-2-4(7)8/h1-3,6,9,21-22H,4-5,7-8,18-19H2;2*1-2H,(H,5,6)(H,7,8)/b;2*2-1-
DescriptionSources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002055/WC500127970.pdfCurator's Comment: description was created based on several sources, including:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf | https://www.medicines.org.uk/emc/PIL.30473.latest.pdf
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002055/WC500127970.pdf
Curator's Comment: description was created based on several sources, including:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf | https://www.medicines.org.uk/emc/PIL.30473.latest.pdf
Pixantrone is a novel anthracenedione. It is a weak inhibitor of topoisomerase II. Pixantrone directly alkylates DNA forming stable DNA adducts and cross-strand breaks. Pixuvri is approved for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin lymphomas. It is used for patients whose cancer does not respond or has returned after they have received other chemotherapy treatments. The most frequent AE were seen in the blood (mainly neutropaenia), gastrointestinal (nausea, abdominal pain, constipation) and respiratory systems (cough, dyspnea). No drug-drug interaction studies have been submitted and no drug interactions have been reported in human subjects
CNS Activity
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002055/WC500127970.pdf
Curator's Comment: Known to be CNS penetrant in rodents. Human data not available.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2311221 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Pixuvri Approved UsePixuvri is used for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin lymphomas. Launch Date2012 |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. | 2001 Jan |
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New immunosuppressants with potential implication in multiple sclerosis. | 2004 Aug 15 |
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The role of pixantrone in the treatment of non-Hodgkin's lymphoma. | 2005 Aug |
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Effects of pixantrone on immune-cell function in the course of acute rat experimental allergic encephalomyelitis. | 2005 Nov |
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Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent. | 2007 |
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Considerations with newer regimens for indolent non-Hodgkin lymphoma. | 2008 Aug |
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Formaldehyde-activated Pixantrone is a monofunctional DNA alkylator that binds selectively to CpG and CpA doublets. | 2008 Jul |
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CE can identify small molecules that selectively target soluble oligomers of amyloid beta protein and display antifibrillogenic activity. | 2009 Apr |
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Pixantrone maleate for non-Hodgkin's lymphoma. | 2009 Nov |
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Pixantrone for the treatment of aggressive non-Hodgkin lymphoma. | 2010 Aug |
Patents
Sample Use Guides
The recommended dose is 50 mg/m^2 of pixantrone on day 1, 8 and 15 of each 28-day cycle for up to 6 cycles.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26660439
In separate 72-hour growth-inhibitory assays using direct cell counting, the etoposide-resistant K/VP.5 cells were 21.6-fold cross-resistant to pixantrone, yielding IC50 values of 0.04 and 0.85 uM for K562 and K/VP.5 cells, respectively.
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EU-Orphan Drug |
EU/3/09/722
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EMA ASSESSMENT REPORTS |
PIXUVRI (AUTHORIZED: LYMPHOMA, NON-HODGKIN)
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NCI_THESAURUS |
C582
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P0R64C4CR9
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9937618
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C82398
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144675-97-8
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m8898
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100000124199
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SUB31562
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DBSALT000141
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752341
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WW-63
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CHEMBL167731
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD