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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
53.80 |
| H2O |
5.0 |
9.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
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.
| 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.
1: Almasoudi HH, Nahari MH, Alhazmi AYM, Almasabi SHA, Al-Mansour FSH, Hakami MA. Delineating Pixantrone Maleate's adroit activity against cervical cancer proteins through multitargeted docking-based MM\GBSA, QM-DFT and MD simulation. PLoS One. 2023 Dec 15;18(12):e0295714. doi: 10.1371/journal.pone.0295714. PMID: 38100507; PMCID: PMC10723688.
2: Afowowe TO, Sakurai Y, Urata S, Zadeh VR, Yasuda J. Topoisomerase II as a Novel Antiviral Target against Panarenaviral Diseases. Viruses. 2022 Dec 30;15(1):105. doi: 10.3390/v15010105. PMID: 36680145; PMCID: PMC9866940.
3: Song YZ, Huang ZJ, Luo X, Wang MJ, Zheng JH, Shi J, Deng YH. [Pharmacodynamics of liposomes modified with different chain length of sialic acid derivatives]. Yao Xue Xue Bao. 2016 Feb;51(2):316-24. Chinese. PMID: 29856587.
4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Dec;31(10):661-700. PMID: 20140276.
5: Mukherji D, Pettengell R. Pixantrone maleate for non-Hodgkin's lymphoma. Drugs Today (Barc). 2009 Nov;45(11):797-805. doi: 10.1358/dot.2009.45.11.1438459. PMID: 20126672.
6: Bayés M, Rabasseda X. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jan-Feb;30(1):67-99. PMID: 18389098.
7: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Jul-Aug;27(6):411-61. PMID: 16179960.
8: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Mar;26(2):129-61. PMID: 15071612.
