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

General Information of Drug (ID: DMSOPAU)

• Drug Name: PYRAZOLOACRIDINE Drug Info
• Synonyms: PD-115934; 2-[3-(Dimethylamino)propyl]-9-methoxy-5-nitro-2,6-dihydropyrazolo[3,4,5-kl]acridine; 9-Methoxy-N,N-dimethyl-5-nitro-2,6-dihydropyrazolo[3,4,5-kl]acridine-2-propanamine

Indication

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 339455
  CAS Number: CAS 99009-20-8
  TTD Drug ID: DMSOPAU
  INTEDE Drug ID: DR1850

Molecule-Related Drug Atlas

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	[6]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[5]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[7]
Idarubicin	DMM0XGL	Acute myelogenous leukaemia	2A41	Approved	[5]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[8]
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[5]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[9]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[10]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]

Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[20]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[25]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[27]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	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	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
E3 ubiquitin-protein ligase XIAP	OT24GP9B	XIAP_HUMAN	Drug Response	[4]

References

• [1] ClinicalTrials.gov (NCT00003802) Pyrazoloacridine in Treating Patients With Metastatic Skin or Eye Melanoma. U.S. National Institutes of Health.
• [2] Effect of pyrazoloacridine (NSC 366140) on DNA topoisomerases I and II. Clin Cancer Res. 1998 Mar;4(3):683-91.
• [3] The metabolism of pyrazoloacridine (NSC 366140) by cytochromes p450 and flavin monooxygenase in human liver microsomes. Clin Cancer Res. 2004 Feb 15;10(4):1471-80.
• [4] Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Etoposide, topoisomerase II and cancer.Curr Med Chem Anticancer Agents.2005 Jul;5(4):363-72.
• [7] Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
• [8] Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
• [9] Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
• [10] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [11] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [16] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [19] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [20] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [21] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [22] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [23] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [24] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [25] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [26] 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.
• [27] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [28] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.