Dexrazoxane xHCl (ICRF-187)

Alias: ICRF-187 (ADR-529) HCl; (+)-Razoxane hydrochloride; ADR-529 hydrochloride; Cardioxan; Dexrazoxane HCl, Dexrazoxane hydrochloride; ICRF-187 hydrochloride; Savene; ADR529; ADR-529; ADR 529; ICRF-187; ICRF187; ICRF 187; NSC169780; NSC-169780; NSC 169780; Cardioxan; Cardioxane; US brand names: Totect; Zinecard. Foreign brand names: Cardioxane Savene.
Cat No.:V2005 Purity: ≥98%
Dexrazoxane xHCl (formerly also known as ICRF-187, ADR-529) acts as an intracellular iron chelator, which decreases the formation of superoxide radicals, and is mainly used as a cardioprotective agent.
Dexrazoxane xHCl (ICRF-187) Chemical Structure CAS No.: 149003-01-0
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
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100mg
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Other Forms of Dexrazoxane xHCl (ICRF-187):

  • Dexrazoxane hydrochloride
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Dexrazoxane xHCl (formerly also known as ICRF-187, ADR-529) acts as an intracellular iron chelator, which decreases the formation of superoxide radicals, and is mainly used as a cardioprotective agent. Dextrazoxane, a derivative of EDTA, chelates iron; however, its exact mechanism of action to protect the heart is unknown. The purpose of this medication is to shield the heart from cardiotoxic side effects. Rat cardiac myocytes exposed to higher anthracycline concentrations do not experience necrosis; instead, daunorubicin-induced myocyte apoptosis is prevented by dexrazoxane (10 mM), which is known clinically to limit anthracycline cardiac toxicity.

Biological Activity I Assay Protocols (From Reference)
ln Vitro

Dexrazoxane (10 mM), which is known to clinically limit the cardiac toxicity of anthracyclines, inhibits daunorubicin-induced myocyte apoptosis but not necrosis brought on by higher anthracycline concentrations in rat cardiac myocytes. It is likely that dexrazoxane's cardioprotective effects come from binding iron, either loosely bound or bound to doxorubicin, which prevents or reduces the production of oxygen radicals that damage specific cell components at a given site. In H9C2 cardiomyocytes, doxorubicin-induced DNA damage signal gamma-H2AX is specifically eliminated by dexrazoxane, but not by camptothecin or hydrogen peroxide. Additionally, doxorubicin-induced DNA damage is reduced in tandem with the fast degradation of Top2beta induced by dexrazoxane. Dexrazoxane interferes with Top2beta to counteract doxorubicin-induced DNA damage, which may be related to Top2beta's role in doxorubicin cardiotoxicity.

ln Vivo
Dexrazoxane binds iron to stop the production of superhydroxide radicals, thereby averting mitochondrial damage. It is hydrolyzed to its active form inside cells.
Animal Protocol
N/A
B6D2F1 mice
References

[1]. Cancer Res . 2007 Sep 15;67(18):8839-46.

[2]. Circ Res . 1999 Feb 19;84(3):257-65.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C11H16N4O4.XHCL
Molecular Weight
N/A
CAS #
149003-01-0
Related CAS #
1263283-43-7 (HCl); 24584-09-6; 149003-01-0 (HCl)
SMILES
C[C@@H](CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)C2.Cl
InChi Key
BIFMNMPSIYHKDN-FJXQXJEOSA-N
InChi Code
InChI=1S/C11H16N4O4.ClH/c1-7(15-5-10(18)13-11(19)6-15)2-14-3-8(16)12-9(17)4-14;/h7H,2-6H2,1H3,(H,12,16,17)(H,13,18,19);1H/t7-;/m0./s1
Chemical Name
4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione;hydrochloride
Synonyms
ICRF-187 (ADR-529) HCl; (+)-Razoxane hydrochloride; ADR-529 hydrochloride; Cardioxan; Dexrazoxane HCl, Dexrazoxane hydrochloride; ICRF-187 hydrochloride; Savene; ADR529; ADR-529; ADR 529; ICRF-187; ICRF187; ICRF 187; NSC169780; NSC-169780; NSC 169780; Cardioxan; Cardioxane; US brand names: Totect; Zinecard. Foreign brand names: Cardioxane Savene.
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~60 mg/mL (~196.9 mM)
Water: ~60 mg/mL (~196.9 mM)
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 3 mg/mL (8.79 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 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 3 mg/mL (8.79 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 30.0 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.

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Solubility in Formulation 3: ≥ 3 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: 130 mg/mL (381.02 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.)
Calculator

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Dexrazoxane and the SOD mimetic MnTMPyP inhibit daunorubicin-induced apoptosis. Circ Res. 1999 Feb 19;84(3):257-65.
  • Dexrazoxane reduces doxorubicin-induced DNA damage. Cancer Res. 2007 Sep 15;67(18):8839-46.
  • Dexrazoxane induces proteasomal degradation of Top2β in H9C2 cardiomyocytes. Cancer Res. 2007 Sep 15;67(18):8839-46.
  • Two proposed mechanisms for the antagonistic effect of dexrazoxane on doxorubicin-induced DNA damage. Cancer Res. 2007 Sep 15;67(18):8839-46.
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