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], [2]
Chemoprotection	N.A.	Approved	[3], [4]
Respiratory tract disease	CB7Z	Investigative	[5]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 268.27
  Topological Polar Surface Area (xlogp); -1.4
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [6]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 3.1 mL/min/kg [7]
  Elimination: 42% of drug is excreted from urine in the unchanged form [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [7]
  Metabolism: The drug is metabolized via the enzyme dihydropyrimidine amidohydrolase in the liver and kidney [8]
  Unbound Fraction: The unbound fraction of drug in plasma is 1% [7]
  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 [7]
  Water Solubility: The ability of drug to dissolve in water is measured as 11 mg/mL [6]
• 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

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	[9]
DNA topoisomerase II beta (TOP2B)	TT4NVEM	TOP2B_HUMAN	Inhibitor	[10]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Dihydropyrimidinase-related protein 1 (DRP1) Main DME	DE0EUXB	DPYL1_HUMAN	Substrate	[11]

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]	[22]

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] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076068.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000788)
• [5] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
• [6] BDDCS applied to over 900 drugs
• [7] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [8] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] 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.
• [12] A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.Pharmacogenet Genomics.2014 Feb;24(2):129-32.
• [13] XK469, a selective topoisomerase IIbeta poison. Proc Natl Acad Sci U S A. 1999 October 12; 96(21): 12168-12173.
• [14] Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model. J Med Chem. 1998 Oct 22;41(22):4273-8.
• [15] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [16] Etoposide, topoisomerase II and cancer.Curr Med Chem Anticancer Agents.2005 Jul;5(4):363-72.
• [17] Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
• [18] Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
• [19] Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
• [20] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [21] Design of two etoposide-amsacrine conjugates: topoisomerase II and tubuline polymerization inhibition and relation to cytotoxicity. Anticancer Drug Des. 2000 Dec;15(6):413-21.
• [22] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.