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

General Information of Drug (ID: DM5WDKY)

• Drug Name: TAS-103 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 135413533
  CAS Number: CAS 174634-08-3
  TTD Drug ID: DM5WDKY
  INTEDE Drug ID: DR1813

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	[4]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[5]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[4]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[6]
Idarubicin	DMM0XGL	Acute myelogenous leukaemia	2A41	Approved	[4]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[7]
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[4]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[8]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[9]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[10]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[11]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[12]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[15]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[16]
Metronidazole	DMTIVEN	Abscess		Approved	[17]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[18]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[19]

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
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007714)
• [2] Mechanism of action of the dual topoisomerase-I and -II inhibitor TAS-103 and activity against (multi)drug resistant cells. Cancer Chemother Pharmacol. 2000;45(1):78-84.
• [3] Phase I clinical and pharmacogenetic study of weekly TAS-103 in patients with advanced cancer. J Clin Oncol. 2001 Apr 1;19(7):2084-90.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Etoposide, topoisomerase II and cancer.Curr Med Chem Anticancer Agents.2005 Jul;5(4):363-72.
• [6] Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
• [7] Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
• [8] Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
• [9] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [10] Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
• [11] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
• [12] Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
• [13] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [14] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [15] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [16] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [17] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [18] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [19] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.