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

General Information of Drug (ID: DMBFE4K)

Drug Name

Tirapazamine Drug Info

Synonyms

TPZ; Tirazone; SR-259075; SR-4233; SR-4317; SR-4330; SR-4482; Win-59075

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 3	[1]
Hepatocellular carcinoma	2C12.02	Phase 2	[2]

Cross-matching ID

PubChem CID: 135413511
ChEBI ID: CHEBI:78887
CAS Number: CAS 27314-97-2
TTD Drug ID: DMBFE4K
INTEDE Drug ID: DR1602

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Approved Drug(s)

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Drug(s) Targeting DNA topoisomerase II (TOP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[6]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[7]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[6]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[8]
Idarubicin	DMM0XGL	Acute myelogenous leukaemia	2A41	Approved	[6]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[9]
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[6]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[10]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[11]
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Drug(s) Metabolized By Cytochrome P450 2E1 (CYP2E1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[12]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[16]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[17]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[18]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[19]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[20]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[21]
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Drug(s) Affected By Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[24]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[25]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[26]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[27]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[28]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[29]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[30]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[31]
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Drug(s) Affected By Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[32]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[33]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[34]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[35]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[36]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[37]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[38]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[39]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[40]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[41]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[3]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1)^{Main DME}	DEVDYN7	CP2E1_HUMAN	Substrate	[4]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[5]

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References

1	ClinicalTrials.gov (NCT00262821) Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer. U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
4	Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations. Br J Cancer. 1995 Apr;71(4):780-5.
5	Tirapazamine cytotoxicity for neuroblastoma is p53 dependent. Clin Cancer Res. 2005 Apr 1;11(7):2774-80. doi: 10.1158/1078-0432.CCR-04-2382.
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7	Etoposide, topoisomerase II and cancer.Curr Med Chem Anticancer Agents.2005 Jul;5(4):363-72.
8	Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
9	Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
10	Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
11	Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
12	Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
13	Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
14	Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
15	Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
16	A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
17	The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
18	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
19	Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
20	Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
21	CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
22	p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
23	The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
24	Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
25	Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
26	Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
27	Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
28	Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
29	Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
30	Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
31	Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.
32	Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
33	Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
34	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.
35	Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
36	BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
37	Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
38	Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
39	Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
40	Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
41	Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.