Details of the Drug

General Information of Drug (ID: DMD7X1O)

Drug Name

Dexrazoxane

Synonyms

24584-09-6; Zinecard; (S)-4,4'-(Propane-1,2-diyl)bis(piperazine-2,6-dione); Cardioxane; ICRF-187; Dexrazoxano; Dexrazoxanum; Dextrorazoxane; Dexrazoxanum [INN-Latin]; Dexrazoxano [INN-Spanish]; Desrazoxane; Eucardion; ADR 529; ICRF 187; (+)-(S)-4,4'-Propylenedi-2,6-piperazinedione; Dexrazone; ADR-529; (+)-1,2-Bis(3,5-dioxo-1-piperazinyl)propane; HSDB 7319; UNII-048L81261F; NSC169780; dyzoxane; BRN 5759131; CHEBI:50223; 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione; NSC 169780; AK-72797; Razoxanum; Cardioxane; Dyzoxane; Savene; TopoTect; Totect; Dexrazoxane HCl; Dexrazoxane hydrochloride; ICRF 187 hydrochloride; Cardioxane (TN); Dexrazoxane (TN); Totect (TN); Zinecard (TN); Dexrazoxane (USAN/INN); Dexrazoxane [USAN:BAN:INN]; Soluble ICRF (L-isosomer); Razoxane, (S)-Isomer; Totect, ICRF-187, Zinecard, Cardioxane, Dexrazoxane Hydrochloride;(+)-(S)-4,4'-Propylenedi-2,6-piperazinedione; (+)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane; (S)-(+)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane; 2,6-Piperazinedione, 4,4'-(1-methyl-1,2-ethanediyl)bis-, (+)-(9CI); 4,4'-(2S)-propane-1,2-diyldipiperazine-2,6-dione; 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione hydrochloride; Icrf-187

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Chemoprotection	N.A.	Approved	[2]
Inflammatory breast cancer	2C62	Approved	[3]
Respiratory tract disease	CB7Z	Investigative	[4]
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Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

268.27

Logarithm of the Partition Coefficient (xlogp)

-1.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [5]
Clearance: The drug present in the plasma can be removed from the body at the rate of 3.1 mL/min/kg [6]
Elimination: 42% of drug is excreted from urine in the unchanged form [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [6]
Metabolism: The drug is metabolized via the enzyme dihydropyrimidine amidohydrolase in the liver and kidney []
Unbound Fraction: The unbound fraction of drug in plasma is 1% [6]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.55 L/kg [6]
Water Solubility: The ability of drug to dissolve in water is measured as 11 mg/mL [5]

Chemical Identifiers

Formula: C11H16N4O4
IUPAC Name: 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
Canonical SMILES: C[C@@H](CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)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
InChIKey: BMKDZUISNHGIBY-ZETCQYMHSA-N

Cross-matching ID

PubChem CID: 71384
ChEBI ID: CHEBI:50223
CAS Number: 24584-09-6
DrugBank ID: DB00380
TTD ID: D07XVN
VARIDT ID: DR00417
INTEDE ID: DR1772

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN ; TOP2B_HUMAN	Modulator	[7]
DNA topoisomerase II beta (TOP2B)	TT4NVEM	TOP2B_HUMAN	Inhibitor	[8]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Dihydropyrimidinase-related protein 1 (DRP1)_{Main DME}	DE0EUXB	DPYL1_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dexrazoxane (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Dexrazoxane and Tecfidera.	Multiple sclerosis [8A40]	[11]
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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7330).
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	Dexrazoxane FDA Label
4	Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
5	BDDCS applied to over 900 drugs
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
9	Metabolism of the cardioprotective drug dexrazoxane and one of its metabolites by isolated rat myocytes, hepatocytes, and blood. Drug Metab Dispos. 2005 Jun;33(6):719-25.
10	Investigation of novel dexrazoxane analogue JR-311 shows significant cardioprotective effects through topoisomerase IIbeta but not its iron chelating metabolite. Toxicology. 2017 Dec 1;392:1-10. doi: 10.1016/j.tox.2017.09.012. Epub 2017 Sep 21.
11	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.