Pixantrone (BBR-2778

Alias: BBR-2778; BBR2778; BBR 2778
Cat No.:V0068 Purity: ≥98%
Pixantrone (formerly known as BBR 2778), is a novel, potent aza-anthracenedione analog with anticancer activity with little cardiotoxicity.
Pixantrone (BBR-2778 Chemical Structure CAS No.: 144510-96-3
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of Pixantrone (BBR-2778:

  • Pixantrone HCl
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description

Pixantrone (formerly known as BBR 2778), is a novel, potent aza-anthracenedione analog with anticancer activity with little cardiotoxicity. It functions as a weak inhibitor of topoisomerase II and a DNA intercalator, selectively forming stable DNA adducts at sites of hypermethylation through alkylation. DNA replication is inhibited and tumor cell cytotoxicity is caused when it intercalates into DNA and creates topoisomerase II-mediated DNA strand crosslinks. Despite their importance as oncotherapeutics, anthracene and anthracene derivatives are linked to cumulative and irreversible cardiotoxicity. Pixantrone was created to decrease treatment-related cardiotoxicity without compromising effectiveness. For patients with aggressive non-Hodgkin lymphoma (aNHL), Pixantrone is a less cardiotoxic and more effective treatment than doxorubicin.

Biological Activity I Assay Protocols (From Reference)
Targets
Topoisomerase II
ln Vitro

Pixantrone dimaleate is a novel and potent aza-anthracenedione analog that has little cardiotoxicity and anticancer activity. It was formerly known as BBR 2778. It functions as a DNA intercalator and weak inhibitor of topoisomerase II, selectively forming stable DNA adducts at sites of hypermethylation through alkylation. It enters DNA and causes DNA strand crosslinks mediated by topoisomerase II, which inhibits DNA replication and reduces the cytotoxicity of tumor cells. Important oncotherapeutics, anthracenenes and anthracenecyclines are linked to cumulative and irreversible cardiotoxicity when used. In order to minimize treatment-related cardiotoxicity without sacrificing effectiveness, Pixantrone was created. Patients diagnosed with aggressive non-Hodgkin lymphoma (aNHL) can benefit from a less cardiotoxic and more effective alternative to doxorubicin: Pixantrone. Regardless of cell cycle disruption, pazantrone causes cell death in a number of cancer cell lines. Its IC50 values for T47D, MCF-10A, and OVCAR5 cells are 37.3 nM, 126 nM, and 136 nM, respectively. Pixantrone damages DNA at high concentrations (500 nM), but not at low enough concentrations (100 nM) to cause PANC1 cells to die. In PANC1 cells, Pixantrone (25 or 100 nM) causes severe chromosomal abnormalities and a mitotic catastrophe. Because plicantrone (100 nM) generates merotelic kinetochore attachments that result in chromosome non-disjunction, it may interfere with chromosome segregation. With IC50s of 0.10 μM, 0.56 μM, 0.058 μM, and 4.5 μM, respectively, pazantrone potently inhibits the growth of human leukemia K562 cells, etoposide-resistant K/VP.5 cells, MDCK, and ABCB1-transfected MDCK/MDR cells. Pixantrone (0.01-0.2 μM) acts on topoisomerase IIα to form linear DNA in a concentration-dependent manner. In an enzymatic reducing system, pyrantrone generates semiquinone free radicals; however, it does not do so in a cellular system, probably because of insufficient cellular uptake. Pixantrone (0.01-10 μM) exhibits strong inhibitory effects on the proliferation of T cells that are specific to the rat 97-116 peptide.

ln Vivo
Pixantrone at 27 mg/kg does not exacerbate pre-existing moderate degenerative cardiomyopathy in mice treated with doxorubicin intravenously once every seven days, repeated three times (q7d × 3). After multiple treatment cycles, mice treated with Pixantrone (27 mg/kg) experience minimal cardiotoxicity. Furthermore, in mice given doxorubicin beforehand, Pixantrone causes less mortality than mitoxantrone. Pixantrone (16.25 mg/kg i.v., q7d × 3) affects T cell subpopulations in TAChR-immunized Lewis rats and modifies the responses of lymph node cells (LNCs). Pixantrone also demonstrates therapeutic and preventive effects in rats with experimental autoimmune myasthenia gravis (EAMG).
Cell Assay
Following seeding into 96-well plates, cells are exposed to escalating doses of either doxorubicin or pixantrone for a full 72 hours. Subsequently, the cells are treated with MTS reagent and allowed to incubate for an additional 4 hours at 37°C. The absorbance at 490 nm is then used to calculate the rate of cell proliferation. Every data point is compared to untreated cells for normalcy. Every treatment is administered in triplicate and at least three times.
Animal Protocol
i.v.;16.25 mg/kg i.v, q7d × 3
Mouse and rats
References

[1]. BGP-15 Improves Aspects of the Dystrophic Pathology in mdx and dko Mice with Differing Efficacies in Heart and Skeletal Muscle. Am J Pathol. 2016 Dec;186(12):3246-3260.

[2]. The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction. Sci Transl Med. 2016 Aug 3;8(350):350ra103.

[3]. The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. Nat Commun. 2014 Dec 9;5:5705.

[4]. Improvement of insulin sensitivity by a novel drug candidate, BGP-15, in different animal studies. Metab Syndr Relat Disord. 2014 Mar;12(2):125-31.

[5]. BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Mol Cell Biochem. 2012 Jun;365(1-2):129-37.

[6]. BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase. Biochem Pharmacol. 2000 Apr 15;59(8):937-45.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H19N5O2
Molecular Weight
325.37
Exact Mass
325.15
CAS #
144510-96-3
Appearance
Powder
SMILES
C1=CC(=C2C(=C1NCCN)C(=O)C3=C(C2=O)C=NC=C3)NCCN
InChi Key
PEZPMAYDXJQYRV-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H19N5O2/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/h1-3,6,9,21-22H,4-5,7-8,18-19H2
Chemical Name
6,9-bis(2-aminoethylamino)benzo[g]isoquinoline-5,10-dione
Synonyms
BBR-2778; BBR2778; BBR 2778
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: >100 mg/mL
Water: >100 mg/mL
Ethanol: <1mg/mL
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.0734 mL 15.3671 mL 30.7342 mL
5 mM 0.6147 mL 3.0734 mL 6.1468 mL
10 mM 0.3073 mL 1.5367 mL 3.0734 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Biological Data
  • 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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