Dexrazoxane

Dexrazoxane

File:Dexrazoxane.svg
Systematic (IUPAC) name
4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a609010
Identifiers
CAS Number	24584-09-6 Y
ATC code	V03AF02 (WHO)
PubChem	CID: 71384
IUPHAR/BPS	7330
DrugBank	DB00380 Y
ChemSpider	64479 Y
UNII	048L81261F Y
KEGG	D03730 Y
ChEBI	CHEBI:50223 Y
ChEMBL	CHEMBL1738 Y
Chemical data
Formula	C11H16N4O4
Molecular mass	268.269 g/mol
SMILES O=C2NC(=O)CN(C[C@@H](N1CC(=O)NC(=O)C1)C)C2
InChI InChI=1S/C11H16N4O4/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)/t7-/m0/s1 Y Key:BMKDZUISNHGIBY-ZETCQYMHSA-N Y
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Dexrazoxane hydrochloride (Zinecard by Pfizer in USA and Canada; Cardioxane by Novartis for EU and other countries) is a cardioprotective agent. It was discovered by Kurt Hellmann in 1972. Dexrazoxane is a sterile, pyrogen-free lyophilizate intended for intravenous administration. The IV administration of dexrazoxane is in acidic condition with HCl adjusting the pH.

Uses

Dexrazoxane has been used to protect the heart against the cardiotoxic side effects of chemotherapeutic drugs such as anthracyclines, such as daunorubicin or doxorubicin or other chemotherapeutic agents. However, in July 2011 the US Food and Drug Administration released a statement restricting use only in adult patients with cancer who have received > 300 mg/m2 doxorubicin (an anthracycline) or > 540 mg/m2 epirubicin (another chemotherapeutic agent) and general approval for use for cardioprotection. That showed a possibly higher rate of secondary malignancies and acute myelogenous leukemia in pediatric patients treated for different cancers with both dexrazoxane and other chemotherapeutic agents that are associated with secondary malignancies.

The United States Food and Drug Administration has also approved a dexrazoxane hydrochloride drug, brand name Totect or Savene (developed by TopoTarget), for use as a treatment of extravasation resulting from IV anthracycline chemotherapy. Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.

Mechanism

As a derivative of EDTA, dexrazoxane chelates iron and thus reduces the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals. The exact chelation mechanism is unknown, but it has been postulated that dexrazoxane can be converted into ring-opened form intracellularly and interfere with iron-mediated free radical generation that is in part thought to be responsible for anthryacycline induced cadiomyopathy. It was speculated that dexrazoxane could be used for further investigation to synthesize new antimalarial drugs.