Pixantrone dimaleateProduct ingredient for Pixantrone
- Name
- Pixantrone dimaleate
- Drug Entry
- Pixantrone
Pixantrone is an aza-anthracenedione and DNA intercalator which inhibits topoisomerase II. It is similar in structure to anthracyclines such as mitoxantrone, but exerts fewer toxic effects on cardiac tissue. [2] The lower cardio-toxic effects of pixantrone may be explained, in part, by its redox inactivity [3]. Pixantrone does not bind iron and promotes the formation of reactive oxygen species to a lesser degree than other anthracyclines. It also inhibits doxorubicinol formation in human myocardium. [3] As a result, it is believed to be less cardiotoxic while still exerting efficacy.
Pixantrone was designed to treat relapsed or refractory aggressive non-Hodgkin's lymphoma(NHL) in patients who have failed two prior lines of therapy. [2] For patients suffering from NHL, first line therapies consist of anthracycline containing multi-drug treatments which unfortunately are known to cause irreversible myocardial tissue damage. Patients refractory to treatment, or those who relapse, are discouraged from further anthracycline use due to cumulative cardiotoxicity. Pixantrone dimaleate, administered intravenously, was designed by Cell Therapeutics Incorporated as an alternative second line therapy in refractory or relapsed NHL. It is currently being tested in Phase III trials. [2]
Although pixantrone has not yet received FDA approval in the United States, it has been granted conditional marketing approval by the European Union. Conditional approval was granted by the European Medicines Agency after a phase III EXTEND trial of patients with NHL showed that pixantrone was tolerable and that it resulted in significantly higher complete response rate and progression free survival in comparison to other single chemotherapy agents. However, it is notable that the EXTEND trial was stopped early, leaving the statistical significance of the results in question. Based on this uncertainty, in 2009, the FDA ultimately rejected Cell Therapeutic's initial application for accelerated approval for pixantrone use in relapsed or refractory NHL. Another phase III trial, PIX-R, is now ongoing to clarify pixantrones place in therapy. It will compare pixantrone efficacy to that of gemcitabine. [2]
- Accession Number
- DBSALT000141
- Structure
- Synonyms
- Pixantrone maleate
- UNII
- P0R64C4CR9
- CAS Number
- 144675-97-8
- Weight
- Average: 557.5094
Monoisotopic: 557.175792109 - Chemical Formula
- C25H27N5O10
- InChI Key
- SVAGFBGXEWPNJC-SPIKMXEPSA-N
- InChI
- 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-
- IUPAC Name
- bis((2Z)-but-2-enedioic acid); 6,9-bis[(2-aminoethyl)amino]-5H,10H-benzo[g]isoquinoline-5,10-dione
- SMILES
- [H]\C(=C(/[H])C(O)=O)C(O)=O.[H]\C(=C(/[H])C(O)=O)C(O)=O.NCCNC1=CC=C(NCCN)C2=C1C(=O)C1=C(C=NC=C1)C2=O
- External Links
- PubChem Compound
- 9937618
- ChemSpider
- 8113244
- ChEMBL
- CHEMBL2103844
- Wikipedia
- Pixantrone
- Predicted Properties
Property Value Source Water Solubility 0.494 mg/mL ALOGPS logP 0.57 ALOGPS logP 0.35 Chemaxon logS -2.8 ALOGPS pKa (Strongest Basic) 9.86 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 123.13 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 95.28 m3·mol-1 Chemaxon Polarizability 35.09 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon