 Chemical Structure.png)
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 interacts by alkylating specific DNA hypermethylated sites to form stable DNA adducts.
Physicochemical Properties
| Molecular Formula | C17H19N5O2.2C4H4O4 | |
| Molecular Weight | 557.51 | |
| Exact Mass | 557.18 | |
| Elemental Analysis | C, 53.86; H, 4.88; N, 12.56; O, 28.70 | |
| CAS # | 144675-97-8 | |
| Related CAS # | 144510-96-3; 175989-38-5 (HCl); 144675-97-8 | |
| PubChem CID | 9937618 | |
| Appearance | Brown to black solid powder | |
| Boiling Point | 650ºC at 760mmHg | |
| Flash Point | 346.9ºC | |
| Vapour Pressure | 8.89E-17mmHg at 25°C | |
| LogP | 1.856 | |
| Hydrogen Bond Donor Count | 8 | |
| Hydrogen Bond Acceptor Count | 15 | |
| Rotatable Bond Count | 10 | |
| Heavy Atom Count | 40 | |
| Complexity | 591 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O=C1C2C([H])=C([H])N=C([H])C=2C(C2=C(C([H])=C([H])C(=C21)N([H])C([H])([H])C([H])([H])N([H])[H])N([H])C([H])([H])C([H])([H])N([H])[H])=O.O([H])C(/C(/[H])=C(\[H])/C(=O)O[H])=O |
|
| 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- | |
| Chemical Name | 6,9-bis(2-aminoethylamino)benzo[g]isoquinoline-5,10-dione;(Z)-but-2-enedioic acid | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Topoisomerase II | ||
| ln Vitro |
|
||
| ln Vivo |
|
||
| Cell Assay | Pixantrone or doxorubicin at escalating concentrations is applied to cells seeded into 96-well plates for a duration of 72 hours. Subsequently, the cells are treated with MTS reagent and given a 4-hour incubation period at 37°C. Finally, the absorbance at 490 nm is measured to estimate cell proliferation. For every data point, untreated cells are used as a normal. Every therapy is administered three times at the very least in triplicate. | ||
| Animal Protocol |
|
||
| References |
[1]. Pixantrone induces cell death through mitotic perturbations and subsequent aberrant cell divisions. Cancer Biol Ther. 2015;16(9):1397-406. [2]. Mechanisms of Action and Reduced Cardiotoxicity of Pixantrone; a Topoisomerase II Targeting Agent with Cellular Selectivity for the Topoisomerase IIα Isoform. J Pharmacol Exp Ther. 2016 Feb;356(2):397-409. [3]. Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone. Invest New Drugs. 2007 Jun;25(3):187-95. [4]. Pixantrone (BBR2778) reduces the severity of experimental autoimmune myasthenia gravis in Lewis rats. J Immunol. 2008 Feb 15;180(4):2696-703. |
||
| Additional Infomation |
Pixantrone Dimaleate is the dimaleate salt of 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. Drug Indication Pixuvri is indicated as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas (NHL). The benefit of pixantrone treatment has not been established in patients when used as fifth-line or greater chemotherapy in patients who are refractory to last therapy. Treatment of non-Hodgkin lymphoma |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (1.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (1.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 50 mg/mL (89.68 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7937 mL | 8.9684 mL | 17.9369 mL | |
| 5 mM | 0.3587 mL | 1.7937 mL | 3.5874 mL | |
| 10 mM | 0.1794 mL | 0.8968 mL | 1.7937 mL |