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    Pixantrone dimaleate (BBR-2778)
    Pixantrone dimaleate (BBR-2778)

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    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V0067
    CAS #: 144675-97-8Purity ≥98%

    Description: Pixantrone dimaleate, the dimaleate salt of Pixantrone (formerly known as BBR 2778) and an aza-anthracenedione analog, is a weak topoisomerase II inhibitor and DNA intercalator with anticancer activity with little cardiotoxicity. It acts by forming stable DNA adducts via alkylation with specificity for DNA hypermethylated sites.  

    References:  2007 Jun;25(3):187-95.

    Related CAS: 144510-96-3 (free base); 175989-38-5 (HCl) 

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    Molecular Weight (MW) 557.51
    Formula C17H19N5O2.2C4H4O4
    CAS No. 144675-97-8 (dimaleate)
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: >100 mg/mL
    Water: >100 mg/mL
    Ethanol:<1 mg/mL
    Chemical Name 6,9-bis((2-aminoethyl)amino)benzo[g]isoquinoline-5,10-dione dimaleate
    Synonyms BBR-2778 dimaleate; BBR2778 dimaleate; BBR 2778
    SMILES Code O=C(C1=C(NCCN)C=CC(NCCN)=C12)C3=C(C=NC=C3)C2=O.O=C(O)/C=C\C(O)=O.O=C(O)/C=C\C(O)=O

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    In Vitro

    In vitro activity: Pixantrone dimaleate, the dimaleate salt of Pixantrone (formerly known as BBR 2778), is a novel, potent aza-anthracenedione analog with anticancer activity with little cardiotoxicity. It acts as a weak topoisomerase II inhibitor and DNA intercalator that forms stable DNA adducts via alkylation with specificity for DNA hypermethylated sites. It intercalates into DNA and induces topoisomerase II-mediated DNA strand crosslinks, resulting in inhibition of DNA replication and tumor cell cytotoxicity. Anthracyclines and anthracenediones are important oncotherapeutics, however, their use is associated with irreversible and cumulative cardiotoxicity. Pixantrone was developed to reduce treatment-related cardiotoxicity while retaining efficacy. Pixantrone is more effective and less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL). Pixantrone induces cell death in multiple cancer cell lines independent of cell cycle perturbation, with IC50s of 37.3 nM, 126 nM and 136 nM for T47D, MCF-10A and OVCAR5 cells, respectively. Pixantrone induces DNA damage at high concentrations (500 nM) but not at concentrations (100 nM) sufficient to kill PANC1 cells. Pixantrone (25 or 100 nM) induces severe chromosomal aberrations and mitotic catastrophe in PANC1 cells. Pixantrone (100 nM) may disrupt chromosome segregation because of generating merotelic kinetochore attachments that cause chromosome non-disjunction. Pixantrone potently inhibits growth of human Leukemia K562 cells, etoposide-resistant K/VP.5 cells, MDCK and ABCB1-transfected MDCK/MDR cells, with IC50s of 0.10 μM, 0.56 μM, 0.058 μM and 4.5 μM, respectively. Pixantrone (0.01-0.2 μM) leads to a concentration-dependent formation of linear DNA through acting on topoisomerase IIα. Pixantrone produces semiquinone free radicals in an enzymatic reducing system, although not in a cellular system, most likely due to low cellular uptake. Pixantrone (0.01-10 μM) shows potent inhibitory activities against rat 97-116 peptide-specific T cell proliferation

    Cell Assay: cells are seeded into 96-well plates and treated with increasing concentrations of either pixantrone or doxorubicin for 72 hours. After this time, MTS reagent is added to cells and incubated at 37°C for a further 4 hours. Cell proliferation is then determined by measuring the absorbance at 490 nm. All data points are normalized to untreated cells. All treatments are performed in triplicate and performed a minimum of 3 times.

    In VivoPixantrone at 27 mg/kg does not worsen pre-existing moderate degenerative cardiomyopathy in doxorubicin-pretreated mice, by i.v. one dose every 7 days repeated thrice (q7d × 3). Pixantrone (27 mg/kg) causes minimal cardiotoxic in mice following repeated treatment cycles. Moreover, Pixantrone results in less mortality than mitoxantrone in doxorubicin-pretreated mice. Pixantrone (16.25 mg/kg i.v, q7d × 3) modulates Lymph node cells (LNC) responses, and affacts T cell subpopulations in TAChR-immunized Lewis rats. Pixantrone also shows preventive and therapeutic effect in experimental autoimmune myasthenia gravis (EAMG) rats.
    Animal model Mouse and rats
    Formulation & Dosage i.v.;16.25 mg/kg i.v, q7d × 3
    References  2008 Feb 15;180(4):2696-703;  2007 Jun;25(3):187-95.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    Pixantrone dimaleate

    Comparison of the preventive and therapeutic PIX treatments on EAMG manifestation.  2008 Feb 15;180(4):2696-703.


    Pixantrone dimaleate

    Variations in clinical score and body weight in EAMG rats.  2008 Feb 15;180(4):2696-703.


    Pixantrone dimaleate

    Immunological evaluation of the therapeutic PIX and MTX treatments in EAMG rats.  2008 Feb 15;180(4):2696-703.


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