Dexrazoxane HCl (ICRF-187)

For research use only.

Catalog No.S1222 Synonyms: ADR-529

3 publications

Dexrazoxane HCl (ICRF-187) Chemical Structure

Molecular Weight(MW): 304.73

Dexrazoxane HCl (ICRF-187, ADR-529) is an intracellular iron chelator, which decreases the formation of superoxide radicals, used as a cardioprotective agent; also an inhibitor of topoisomerase II

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Description Dexrazoxane HCl (ICRF-187, ADR-529) is an intracellular iron chelator, which decreases the formation of superoxide radicals, used as a cardioprotective agent; also an inhibitor of topoisomerase II
Targets
Topo II [6]
(Cell-free assay)
In vitro

Dexrazoxane (10 mM), known clinically to limit anthracycline cardiac toxicity, prevents daunorubicin-induced myocyte apoptosis, but not necrosis induced by higher anthracycline concentrations in rat cardiac myocytes. [1] Dexrazoxane presumably exerts its cardioprotective effects by either binding free or loosely bound iron, or iron complexed to doxorubicin, thus preventing or reducing site-specific oxygen radical production that damages cellular components. [2] Dexrazoxane specifically abolishes the DNA damage signal gamma-H2AX induced by doxorubicin, but not camptothecin or hydrogen peroxide, in H9C2 cardiomyocytes. Dexrazoxane also induces rapid degradation of Top2beta, which paralleles the reduction of doxorubicin-induced DNA damage. Dexrazoxane antagonizes doxorubicin-induced DNA damage through its interference with Top2beta, which could implicate Top2beta in doxorubicin cardiotoxicity. [3] Dexrazoxane is hydrolyzed to its active form intracellularly and binds iron to prevent the formation of superhydroxide radicals, thus preventing mitochondrial destruction. [4]

Assay
Methods Test Index PMID
Western blot
p-Chk1 / Chk1 / p-Chk2 / ChK2 ; 

PubMed: 25521189     


Phosphorylations of Chk1 at Ser317 (pChk1) and Chk2 at Thr68 (pChk2) were detected by Western blot. Total Chk1 and Chk2 were used as loading controls.

ATF3 / TOP2A ; 

PubMed: 25521189     


HTETOP cells expressing (+TOP2A) or depleted of TOP2A (−TOP2A) by tetracycline pre-treatment were treated with increasing concentrations of dexrazoxane (DRZ) for 24 h (A) or with 100 μM dexrazoxane for the indicated time periods (B). ATF3 and TOP2A protein levels were analysed by Western blot.

TOPOIIα / TOPOIIβ / TOPO I / PABP2 ; 

PubMed: 14978217     


Topoisomerase II is selectively retained by ICRF-187. HeLa cells exposed to ICRF-187 (50 μg/ml, 15 min) or drug solvent alone (controls) were salt-detergent extracted according to the DRT procedure, lysed for SDS-PAGE, and immunoblotted for topo IIα, topo IIβ, topo I, PABP2, and tubulin (ECL method).

25521189 14978217
In vivo Dexrazoxane combined with doxorubicin, daunorubicin, or idarubicin reduces the tissue lesions in B6D2F1 mice (expressed as area under the curve of wound size times duration) by 96%, 70%, and 87%, respectively. Dexrazoxane combined with doxorubicin, daunorubicin, or idarubicin results in a statistically significant reduction in the fraction of mice with wounds as well as the duration of wounds. [5]

Protocol

Cell Research:

[6] 

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  • Cell lines: neonatal rat cardiomyocytes
  • Concentrations: 30 μM
  • Incubation Time: 3 h
  • Method:

    Neonatal rat cardiomyocytes are pre-incubated with dexrazoxane (DEX), sobuzoxane (SOB) or merbarone (MER) for 3 h and then incubated with anthracyclines daunorubicin or doxorubicin for 3 h following a 48-h anthracycline-free period or for 48 h with hydrogen peroxide (H2O2). 


    (Only for Reference)
Animal Research:

[7]

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  • Animal Models: female B6D2FI
  • Dosages: 62.5 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 60 mg/mL warmed (196.89 mM)
Water 60 mg/mL warmed (196.89 mM)
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 304.73
Formula

C11H16N4O4.HCl

CAS No. 149003-01-0
Storage powder
in solvent
Synonyms ADR-529
Smiles Cl.CC(CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)C2

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Topoisomerase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID