| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Topoisomerase
Bisantrene exerts its antitumor effects through multiple mechanisms: DNA intercalation (inserting itself between DNA bases, disrupting normal base pairing and inhibiting replication); topoisomerase II inhibition; and induction of DNA single-strand breaks, DNA-protein cross-links. It is also a Rac1 inhibitor. |
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| ln Vitro |
On oligopurine-oligopyrimidine sequences, bisantrene diHClide enhances DNase I cleavage, whereas on alternating purine-pyrimidine sequences, it somewhat diminishes cleavage activity [1]. The incorporation of [3H]uridine into RNA and [3H]thymidine into DNA is inhibited by bisantrene diHClide [2].
In vitro, bisantrene intercalates into DNA and disrupts DNA configuration, leading to DNA single-strand breaks, DNA-protein cross-links, and DNA replication inhibition. It inhibits topoisomerase II activity, disrupting transcription and replication in rapidly dividing cancer cells. It has shown anticancer activity against various cancer cell lines. |
| ln Vivo |
A number of experimental cancers, such as P388 leukemia, L1210 leukemia, Liebermann's plasmacytoma, B16 melanoma, colon neoplasia 26, and Ridgway osteosarcoma, respond well to the antineoplastic drug bisantrene diHClide [3]. The effectiveness of bisantrene hydrochloride varies between 1.56 and 150 mg/kg, contingent upon the tumor model employed, treatment frequency, modality, and schedule [3]. Macrophages were pretreated with bisantrene hydrochloride (25, 50, and 100 mg/kg; intraperitoneally; once), and animals injected with P815 tumor cells shown anticancer effects [3]. Neo mice are given dose-dependent doses of bisantrene diHClide (10-150 mg/kg; i.v.; once) to cause leukopenia. Bisantrene hydrochloride toxicity targeting B cells and macrophages [4].
In vivo, bisantrene has demonstrated significant antitumor activity and is particularly effective against metastatic breast cancer. It has been used in the treatment of various cancers including leukemia, breast cancer, and ovarian cancer. Its relatively low cardiotoxicity compared to other anthracyclines is a notable advantage. |
| Enzyme Assay |
In ETN buffer (1 mM EDTA, 10 mM Tris, pH 7.0, with NaCl to obtain the desired ionic strength), measurements are performed at 25°C. Spectrophotometric or fluorometric methods are used to observe binding in the ligand absorption or emission region, respectively, following the addition of scalar quantities of DNA to a newly made drug solution. The range of bound drug fractions is 0.15-0.85 in order to prevent significant systematic errors that could arise from experimental errors in extinction coefficients or fluorescence quantum yield. Data are assessed. A Perkin-Elmer Lambda 5 apparatus and an MPF66 fluorometer, both of which have a Haake F3-C thermostat, are used for spectroscopic measurements[1].
In vitro assays for bisantrene typically involve evaluating DNA intercalation by measuring changes in DNA melting temperature, circular dichroism, or fluorescence quenching. Topoisomerase II inhibition is assessed using DNA relaxation or decatenation assays. Cell-free systems may use purified DNA and topoisomerase II enzymes. Binding affinity to DNA is measured by spectrophotometric or fluorometric methods. |
| Cell Assay |
Cell-based assays for bisantrene involve culturing cancer cell lines (e.g., leukemia, breast cancer, ovarian cancer) in appropriate media. Cells are treated with bisantrene at concentrations ranging from 0.1-100 µM for 24-72 hours. Cell viability is assessed by MTT, CCK-8, or colony formation assays. DNA damage is evaluated by comet assay or γ-H2AX staining. Apoptosis is measured by flow cytometry using Annexin V/PI staining.
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| Animal Protocol |
In vivo animal experiments for bisantrene typically involve administration to tumor-bearing mice (xenograft models) via intravenous or intraperitoneal injection at doses ranging from 1-50 mg/kg. Tumor volume is monitored over time. Cardiotoxicity is assessed by echocardiography or histopathological examination of heart tissue. MDR1-mediated resistance is studied using P-glycoprotein-overexpressing tumor models.
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| ADME/Pharmacokinetics |
Bisantrene HCl has a molecular weight of approximately 500-550. As a small molecule DNA intercalator, it is expected to distribute widely in tissues. It is metabolized in the liver and excreted via bile and urine. Its relatively low cardiotoxicity compared to anthracyclines is clinically significant. Detailed PK parameters are available in clinical pharmacology literature.
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| Toxicity/Toxicokinetics |
Bisantrene HCl exhibits relatively low cardiotoxicity compared to other anthracycline chemotherapeutic drugs. This is a significant clinical advantage. Common toxicities may include myelosuppression, gastrointestinal effects, and local reactions at the injection site. Comprehensive toxicological evaluation has been conducted in preclinical and clinical studies.
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| References |
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| Additional Infomation |
Bissatropine hydrochloride is the hydrochloride salt of anthraquinone antitumor drug. Bissatropine can intercalate into and disrupt the helical structure of DNA, leading to single-strand breaks and DNA-protein cross-links, thereby inhibiting DNA replication. Its activity is similar to doxorubicin, but unlike doxorubicin, it does not have cardiotoxicity.
Bisantrene HCl (CAS#: 71439-68-4) is a synthetic anthraquinone derivative and potent anticancer agent. It is a topoisomerase II inhibitor and DNA intercalator. It has been used in the treatment of leukemia, breast cancer, and ovarian cancer. It is also a Rac1 inhibitor and model compound for studying P-glycoprotein-mediated multidrug resistance (MDR1). It shows relatively low cardiotoxicity. |
| Molecular Formula |
C22H24CL2N8
|
|---|---|
| Molecular Weight |
471.38556
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| Exact Mass |
434.173
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| Elemental Analysis |
C, 56.06; H, 5.13; Cl, 15.04; N, 23.77
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| CAS # |
71439-68-4
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| Related CAS # |
Bisantrene;78186-34-2
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| PubChem CID |
6917792
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| Appearance |
Brown to reddish brown solid powder
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| Boiling Point |
646.3ºC at 760 mmHg
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| Flash Point |
344.7ºC
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| LogP |
2.871
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
630
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.Cl.C1CN=C(N/N=C/C2C3=CC=CC=C3C(/C=N/NC3NCCN=3)=C3C=CC=CC=23)N1
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| InChi Key |
KINULKKPVJYRON-PVNXHVEDSA-N
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| InChi Code |
InChI=1S/C22H22N8.2ClH/c1-2-6-16-15(5-1)19(13-27-29-21-23-9-10-24-21)17-7-3-4-8-18(17)20(16)14-28-30-22-25-11-12-26-22;;/h1-8,13-14H,9-12H2,(H2,23,24,29)(H2,25,26,30);2*1H/b27-13+,28-14+;;
|
| Chemical Name |
N-[(E)-[10-[(E)-(4,5-dihydro-1H-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1H-imidazol-2-amine;dihydrochloride
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| Synonyms |
NSC337766; CL-216942; NSC 337766; CL216942; CL 216942; NSC-337766
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~5 mg/mL (~10.6 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1214 mL | 10.6069 mL | 21.2139 mL | |
| 5 mM | 0.4243 mL | 2.1214 mL | 4.2428 mL | |
| 10 mM | 0.2121 mL | 1.0607 mL | 2.1214 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.
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.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04989335 | Recruiting | Drug: Bisantrene Drug: Fludarabine |
Myelogenous Leukemia, Acute | Sheba Medical Center | August 2, 2021 | Phase 2 |
| NCT03820908 | Completed | Drug: Bisantrene | Allogeneic Stem Cell Transplantation Acute Myelogenous Leukemia |
Sheba Medical Center | July 18, 2019 | Phase 2 |
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