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Pixantrone(BBR-2778
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Pixantrone(BBR-2778图片
CAS NO:144510-96-3
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 325.37
Formula C17H19N5O2
CAS No. 144510-96-3 (free base);
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 Name6,9-bis((2-aminoethyl)amino)benzo[g]isoquinoline-5,10-dione
SynonymsBBR-2778; BBR2778; BBR 2778
SMILES CodeO=C(C1=C(NCCN)C=CC(NCCN)=C12)C3=C(C=NC=C3)C2=O
实验参考方法
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 J Immunol. 2008 Feb 15;180(4):2696-703; Invest New Drugs. 2007 Jun;25(3):187-95.