Pixantrone Maleate
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MedKoo CAT#: 202250

CAS#: 144675-97-8 (maleate)

Description: Pixantrone is a synthetic, noncardiotoxic aza-anthracenedione analogue with potential antineoplastic activity. Pixantrone intercalates into DNA and induces topoisomerase II-mediated DNA strand crosslinks, resulting in inhibition of DNA replication and tumor cell cytotoxicity. Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL).


Chemical Structure

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Pixantrone Maleate
CAS# 144675-97-8 (maleate)

Theoretical Analysis

MedKoo Cat#: 202250
Name: Pixantrone Maleate
CAS#: 144675-97-8 (maleate)
Chemical Formula: C25H27N5O10
Exact Mass:
Molecular Weight: 557.52
Elemental Analysis: C, 53.86; H, 4.88; N, 12.56; O, 28.70

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
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Related CAS #: 144675-97-8 (maleate)   144510-96-3 (free base)   175989-38-5 (HCl)    

Synonym: BBR 2778; BBR2778; BBR-2778; Pixantrone; Pixantrone Maleate.

IUPAC/Chemical Name: 6,9-bis((2-aminoethyl)amino)benzo[g]isoquinoline-5,10-dione dimaleate

InChi Key: SVAGFBGXEWPNJC-SPIKMXEPSA-N

InChi Code: 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-

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

Appearance: Brown to black solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO and water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Pixantrone dimaleate is a topoisomerase II inhibitor and DNA intercalator, with anti-tumor activity.
In vitro activity: To test whether the strong anti-proliferative activity of PIX (pixantrone) resulted also in cytotoxicity, the metabolic activity of mitochondria of the myeloma cell lines was measured after 72 h of incubation with PIX in comparison to Dox. PIX dose-dependently inhibited the metabolic activity of myeloma cell lines (Fig.2a). The IC50 for the inhibition was cell line-dependent and in the range of 0.5–5 μM. The cell lines AMO-1 and KMS-12-BM (IC50 at 0.5 μM) were more sensitive to PIX treatment than the other cell lines. To further evaluate the cytotoxic activity, flow cytometry analyses were performed 48 h and 7 days after PIX treatment. After 48 h, a concentration of 0.25 μM PIX reduced the viability of the cell line KMS-12-BM to 75.3 ± 5.4%, whereas 5 μM decreased it to 45.4 ± 6.7% (data not shown). Apoptosis induction, however, was observed only after a 7-day incubation (Fig.33). The ability of PIX to induce cell death of primary plasma cells from patients was assessed after a 24-h incubation period in vitro. PIX dose-dependently diminished the extent of the cells alive of two patients with refractory relapsed MM (multiple myeloma) and five patients with denovo or secondary PCL. At 2.5 μM, the proportion of plasma cells alive was reduced to 67.9 ± 10.4% of control without PIX (Fig.5a). From these data, we conclude that systematic investigations of the clinical usefulness of pixantrone in the framework of controlled clinical trials are clearly indicated. Reference: Ann Hematol. 2019; 98(11): 2569–2578. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848044/
In vivo activity: Pixantrone was tested against eight PPTP solid tumor xenografts using a dose of 7.5 mg/kg administered intravenously q4d x 3. This dose was based on toxicity testing in non-tumored SCID mice. The planned treatment and observation period was 6 weeks. Toxicity was not observed in either treated or control groups at the 7.5 mg/kg dose. Eight of 8 tested xenograft models were considered evaluable for efficacy. Pixantrone induced significant differences in event free survival (EFS) distribution compared to control in 25% (2 of 8) of the evaluable solid tumor xenografts, Table II. Pixantrone induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 12.5% (1 of 8) evaluable solid tumor xenografts. An objective response (KT-10, Wilms tumor) was observed in 1 of 8 solid tumor xenografts. In summary, pixantrone showed tumor regressing activity against a Wilms tumor xenograft. Reference: Pediatr Blood Cancer. 2014 May; 61(5): 922–924. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951603/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 30.0 53.8
H2O 5.0 9.0

Preparing Stock Solutions

The following data is based on the product molecular weight 557.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Willenbacher E, Jöhrer K, Willenbacher W, Flögel B, Greil R, Kircher B. Pixantrone demonstrates significant in vitro activity against multiple myeloma and plasma cell leukemia. Ann Hematol. 2019 Nov;98(11):2569-2578. doi: 10.1007/s00277-019-03797-6. Epub 2019 Oct 18. PMID: 31628518; PMCID: PMC6848044. 2. Beeharry N, Di Rora AG, Smith MR, Yen TJ. Pixantrone induces cell death through mitotic perturbations and subsequent aberrant cell divisions. Cancer Biol Ther. 2015;16(9):1397-406. doi: 10.1080/15384047.2015.1070979. PMID: 26177126; PMCID: PMC4621998. 3. . Kurmasheva RT, Reynolds CP, Kang MH, Allievi C, Houghton PJ, Smith MA. Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2014 May;61(5):922-4. doi: 10.1002/pbc.24800. Epub 2013 Oct 26. PMID: 24166988; PMCID: PMC3951603. 4. Ubiali F, Nava S, Nessi V, Longhi R, Pezzoni G, Capobianco R, Mantegazza R, Antozzi C, Baggi F. Pixantrone (BBR2778) reduces the severity of experimental autoimmune myasthenia gravis in Lewis rats. J Immunol. 2008 Feb 15;180(4):2696-703. doi: 10.4049/jimmunol.180.4.2696. PMID: 18250482.
In vitro protocol: 1. Willenbacher E, Jöhrer K, Willenbacher W, Flögel B, Greil R, Kircher B. Pixantrone demonstrates significant in vitro activity against multiple myeloma and plasma cell leukemia. Ann Hematol. 2019 Nov;98(11):2569-2578. doi: 10.1007/s00277-019-03797-6. Epub 2019 Oct 18. PMID: 31628518; PMCID: PMC6848044. 2. Beeharry N, Di Rora AG, Smith MR, Yen TJ. Pixantrone induces cell death through mitotic perturbations and subsequent aberrant cell divisions. Cancer Biol Ther. 2015;16(9):1397-406. doi: 10.1080/15384047.2015.1070979. PMID: 26177126; PMCID: PMC4621998.
In vivo protocol: 1. Kurmasheva RT, Reynolds CP, Kang MH, Allievi C, Houghton PJ, Smith MA. Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2014 May;61(5):922-4. doi: 10.1002/pbc.24800. Epub 2013 Oct 26. PMID: 24166988; PMCID: PMC3951603. 2. Ubiali F, Nava S, Nessi V, Longhi R, Pezzoni G, Capobianco R, Mantegazza R, Antozzi C, Baggi F. Pixantrone (BBR2778) reduces the severity of experimental autoimmune myasthenia gravis in Lewis rats. J Immunol. 2008 Feb 15;180(4):2696-703. doi: 10.4049/jimmunol.180.4.2696. PMID: 18250482.

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1: Landells LJ, Prescott C, Hay N, Sutcliffe F, Stevens A. NICE guidance on pixantrone monotherapy for multiply relapsed or refractory aggressive non-Hodgkin lymphoma. Lancet Oncol. 2014 Apr;15(4):381-2. PubMed PMID: 24818252.

2: She Z, Zhang T, Wang X, Li X, Song Y, Cheng X, Huang Z, Deng Y. The anticancer efficacy of pixantrone-loaded liposomes decorated with sialic acid-octadecylamine conjugate. Biomaterials. 2014 Jun;35(19):5216-25. doi: 10.1016/j.biomaterials.2014.03.022. Epub 2014 Apr 2. PubMed PMID: 24703714.

3: Longo M, Torre PD, Allievi C, Morisetti A, Al-Fayoumi S, Singer JW. Tolerability and toxicological profile of pixantrone (Pixuvri(®)) in juvenile mice. Comparative study with doxorubicin. Reprod Toxicol. 2014 Mar 3;46C:20-30. doi: 10.1016/j.reprotox.2014.02.006. [Epub ahead of print] PubMed PMID: 24602559.

4: Kurmasheva RT, Reynolds CP, Kang MH, Allievi C, Houghton PJ, Smith MA. Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2014 May;61(5):922-4. doi: 10.1002/pbc.24800. Epub 2013 Oct 26. PubMed PMID: 24166988; PubMed Central PMCID: PMC3951603.

5: Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, Myint H, Saleh A, Singer J, Wilhelm M, van der Jagt R. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013 Oct;24(10):2618-23. doi: 10.1093/annonc/mdt289. Epub 2013 Aug 14. PubMed PMID: 23946328.

6: Péan E, Flores B, Hudson I, Sjöberg J, Dunder K, Salmonson T, Gisselbrecht C, Laane E, Pignatti F. The European Medicines Agency review of pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's B-cell lymphomas: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist. 2013;18(5):625-33. doi: 10.1634/theoncologist.2013-0020. Epub 2013 Apr 24. PubMed PMID: 23615696; PubMed Central PMCID: PMC3662855.

7: Marolda R, Ruocco C, Cordiglieri C, Toscani C, Antozzi C, Mantegazza R, Baggi F. Differential targeting of immune-cells by Pixantrone in experimental myasthenia gravis. J Neuroimmunol. 2013 May 15;258(1-2):41-50. doi: 10.1016/j.jneuroim.2013.02.021. Epub 2013 Mar 21. PubMed PMID: 23523328.

8: Papadatos-Pastos D, Pettengell R. Pixantrone: merging safety with efficacy. Expert Rev Hematol. 2013 Feb;6(1):25-33. doi: 10.1586/ehm.12.61. Review. PubMed PMID: 23373776.

9: Salvatorelli E, Menna P, Paz OG, Chello M, Covino E, Singer JW, Minotti G. The novel anthracenedione, pixantrone, lacks redox activity and inhibits doxorubicinol formation in human myocardium: insight to explain the cardiac safety of pixantrone in doxorubicin-treated patients. J Pharmacol Exp Ther. 2013 Feb;344(2):467-78. doi: 10.1124/jpet.112.200568. Epub 2012 Nov 28. PubMed PMID: 23192654.