Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMD7X1O)

• Drug Name: Dexrazoxane Drug Info
• 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]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 71384
  ChEBI ID: CHEBI:50223
  CAS Number: CAS 24584-09-6
  TTD Drug ID: DMD7X1O
  VARIDT Drug ID: DR00417
  INTEDE Drug ID: DR1772

Molecule-Related Drug Atlas

Drug(s) Targeting DNA topoisomerase II beta (TOP2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XK-469	DMVYO41	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
XB-947	DM1UIOA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
A-62176	DM4WT7Z	N. A.	N. A.	Terminated	[11]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[12]
3'-THIO-THYMIDINE-5'-PHOSPHATE	DM5SM8X	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting DNA topoisomerase II (TOP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[5]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[13]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[5]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[14]
Idarubicin	DMM0XGL	Acute myelogenous leukaemia	2A41	Approved	[5]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[15]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[16]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[17]
Amsacrine	DMZKYIV	Acute lymphoblastic leukaemia	2A85	Approved	[18]

Drug(s) Affected By DNA topoisomerase 2-alpha (TOP2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[22]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[24]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[25]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[28]

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	[5]
DNA topoisomerase II beta (TOP2B)	TT4NVEM	TOP2B_HUMAN	Inhibitor	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Dihydropyrimidinase-related protein 1 (DRP1) Main DME	DE0EUXB	DPYL1_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Gene/Protein Processing	[8]

References

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• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] 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.
• [8] 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.
• [9] A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.Pharmacogenet Genomics.2014 Feb;24(2):129-32.
• [10] XK469, a selective topoisomerase IIbeta poison. Proc Natl Acad Sci U S A. 1999 October 12; 96(21): 12168-12173.
• [11] Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model. J Med Chem. 1998 Oct 22;41(22):4273-8.
• [12] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [13] Etoposide, topoisomerase II and cancer.Curr Med Chem Anticancer Agents.2005 Jul;5(4):363-72.
• [14] Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
• [15] Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
• [16] Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
• [17] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [18] 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.
• [19] Incidence of mutation and deletion in topoisomerase II alpha mRNA of etoposide and mAMSA-resistant cell lines. Jpn J Cancer Res. 2001 Oct;92(10):1133-7. doi: 10.1111/j.1349-7006.2001.tb01069.x.
• [20] HU-331 and Oxidized Cannabidiol Act as Inhibitors of Human Topoisomerase II and . Chem Res Toxicol. 2018 Feb 19;31(2):137-144. doi: 10.1021/acs.chemrestox.7b00302. Epub 2018 Jan 8.
• [21] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [22] Interactions between the etoposide derivative F14512 and human type II topoisomerases: implications for the C4 spermine moiety in promoting enzyme-mediated DNA cleavage. Biochemistry. 2011 Apr 19;50(15):3240-9. doi: 10.1021/bi200094z. Epub 2011 Mar 28.
• [23] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [24] The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
• [25] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [26] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [27] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [28] Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity. Int J Gynecol Cancer. 2006 Jul-Aug;16(4):1552-6. doi: 10.1111/j.1525-1438.2006.00626.x.