Dexrazoxane
|
Catalog No.GC10655
One-Click Copy Product Info
|
Dexrazoxane is a hydrophilic ring-closed analog of iron chelator ethylenediaminetetraacetic acid and also a strong inhibitor of topoisomerase II with IC50 value of 10µM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 24584-09-6
Sample solution is provided at 25 µL, 10mM.
Dexrazoxane is a hydrophilic ring-closed analog of iron chelator ethylenediaminetetraacetic acid and also a strong inhibitor of topoisomerase II with IC50 value of 10µM[1]. Dexrazoxane is the only current FDA approved medication to tackle cardiotoxicity. The mechanism of action in which Dexrazoxane is cardioprotective is by halting necroptosis in cardiomyocytes after anthracycline therapy and concurrently binds with iron and reduces the formation of anthracycline-iron complexes and reactive oxygen species[2].
In vitro, CHO cells were incubated with Dexrazoxane (100µM) for 0.5 or 20h, followed by bleomycin treatment for a further 72h. The cell growth inhibitory effects of bleomycin were unaffected by pretreating CHO cells with Dexrazoxane. Dexrazoxane did not decrease bleomycin-induced inhibition of growth of CHO cells in spite of the ability of the Dexrazoxane metabolite ADR-925 to displace either Fe2+ or Fe3+ from its complex with bleomycin[3]. Neonatal mouse ventricular myocytes (NMVMs) were pretreated with 200µM Dexrazoxane 4h before 0.5µM of doxorubicin hydrochloride treatment, Dexrazoxane exerted a protective effect against doxorubicin-induced cardiotoxicity through attenuating both apoptosis and necroptosis by the inhibition of p38MAPK/NF-kB pathways in cardiomyocytes[4]. HTETOP cells were derived from the human fibrosarcoma cell line HT1080 through the deletion of both endogenous TOP2A alleles and the insertion of a tetracycline-repressible TOP2A transgene. TOP2A-expressing HTETOP cells were treated with 100μM Dexrazoxane for 24h. Dexrazoxane exposure induced topoisomerase IIα (TOP2A)-dependent cell death, γ-H2AX accumulation and increased tail moment in neutral comet assays[5].
In vivo, 6-OHDA induced Parkinson’s disease mouse models were Intraperitoneally administrated with Dexrazoxane (1.5, 5, 15mg/kg/day) for 3 weeks. Dexrazoxane ameliorated dopaminergic neuronal degeneration in Parkinson’s disease models. Dexrazoxane served as a potential neuroprotectant to treat neurotoxin-induced neurodegeneration via attenuation of oxidative stress and ER stress, as well as the suppression of systemic inflammation in both peripheral tissues and brain[6]. Doxorubicin-induced nephropathy rat models was injected intravenously with Dexrazoxane (25mg/kg) once a week for 5 weeks. Dexrazoxane pretreatment markedly raised the survival rate and improved the renal dysfunction in doxorubicin-treated rats. Dexrazoxane ameliorated doxorubicin-induced histopathological lesion of glomerular and tubular and apoptosis. Dexrazoxane restored the oxidant/antioxidant balance via regulating the levels of Malondialdehyde (MDA), superoxide dismutase (SOD), and antioxidant capacity[7].
References:
[1] Hasinoff B B, Herman E H. Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol. 2007;7(2):140-4.
[2] Rahimi P, Barootkoob B, ElHashash A, Nair A. et al. Efficacy of dexrazoxane in Cardiac Protection in Pediatric Patients Treated With Anthracyclines. Cureus. 2023 Apr 8;15(4):e37308.
[3] Xing Wu X, Patel D, Hasinoff B B, et al. The iron chelating cardioprotective prodrug dexrazoxane does not affect the cell growth inhibitory effects of bleomycin. J Inorg Biochem. 2004 Nov;98(11):1818-23.
[4] Yu X X, Ruan Y, Huang X Q, et al. Dexrazoxane ameliorates doxorubicin-induced cardiotoxicity by inhibiting both apoptosis and necroptosis in cardiomyocytes. Biochem Biophys Res Commun. 2020 Feb 26;523(1):140-146.
[5] Deng S, Yan T D, Nikolova T, et al. The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells. Br J Pharmacol. 2015 May;172(9):2246-57.
[6] Mei M, Zhou Y Z, Liu M D, et al. Antioxidant and anti-inflammatory effects of dexrazoxane on dopaminergic neuron degeneration in rodent models of Parkinson's disease. Neuropharmacology. 2019 Dec 1;160:107758.
[7] Hu H H, Xie C P, Weng Z P, et al. Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats. Pharmacology. 2022;107(3-4):206-215.
| Cell experiment [1]: | |
Cell lines | Neonatal mouse ventricular myocytes (NMVMs) |
Preparation Method | Cells were seeded in 96-well plates, the cells were divided into four groups: Con groups were treated with DMSO alone as control, DOX group were treated with 0.5µM of doxorubicin hydrochloride, DOX + DEX group were pretreated with 200µM Dexrazoxane 4h before 0.5µM of doxorubicin hydrochloride treatment, and DEX group were treated with 200µM Dexrazoxane. |
Reaction Conditions | 200µM; 4h |
Applications | Dexrazoxane exerts a protective effect against doxorubicin-induced cardiotoxicity through attenuating both apoptosis and necroptosis by the inhibition of p38MAPK/NF-kB pathways in cardiomyocytes. |
| Animal experiment [2]: | |
Animal models | Male SpragueDawley (SD) rats |
Preparation Method | Unilateral injection of 6-OHDA (8μg 6-OHDA hydrochloride in 4μL of 0.02% ascorbic acid saline solution) was performed in the left striatum of male Sprague Dawley (SD) rats. 6-OHDA-lesioned rats with Dexrazoxane (1.5, 5, 15mg/kg/day, i.p.) for 3 weeks. L-DOPA (10mg/kg/day) was used as a positive control in the present study. |
Dosage form | 1.5, 5, 15mg/kg/day; i.p; 3 weeks |
Applications | Dexrazoxane ameliorates dopaminergic neuronal degeneration in Parkinson’s disease models. Dexrazoxane served as a potential neuroprotectant to treat neurotoxin-induced neurodegeneration via attenuation of oxidative stress and ER stress, as well as the suppression of systemic inflammation in both peripheral tissues and brain. |
References: | |
| Cas No. | 24584-09-6 | SDF | |
| Synonyms | ICRF 187, NSC 169780 | ||
| Chemical Name | 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione | ||
| Canonical SMILES | CC(CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)C2 | ||
| Formula | C11H16N4O4 | M.Wt | 268.27 |
| Solubility | ≥ 12mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.7276 mL | 18.6379 mL | 37.2759 mL |
| 5 mM | 745.5 μL | 3.7276 mL | 7.4552 mL |
| 10 mM | 372.8 μL | 1.8638 mL | 3.7276 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 1 reference(s) in Google Scholar.)