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

General Information of Drug (ID: DM31ZQM)

• Drug Name: Tegafur Drug Info
• Synonyms: Tegafur (Fluoropyrimidine)

Indication

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

• Cross-matching ID:
  PubChem CID: 5386
  ChEBI ID: CHEMBL32188
  CAS Number: CAS 17902-23-7
  TTD Drug ID: DM31ZQM
  INTEDE Drug ID: DR1539

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[2]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[6]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[8]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[9]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[11]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[13]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[14]

Drug(s) Metabolized By Cytochrome P450 2A6 (CYP2A6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[2]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[4]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[4]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[17]
Metronidazole	DMTIVEN	Abscess		Approved	[18]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[19]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[4]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[21]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[28]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[29]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[24]

Drug(s) Metabolized By Cytochrome P450 2E1 (CYP2E1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[30]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[31]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[32]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[33]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[4]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[34]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[35]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[36]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[2]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[37]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[37]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[4]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[38]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[39]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[40]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[37]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[41]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[2]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Substrate	[3]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[4]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[2]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Thymidylate synthase	OTXTG0C7	TYSY_HUMAN	Drug Response	[5]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] 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.
• [3] Rapid development of S-1 in the west for therapy of advanced gastric carcinoma. Gan To Kagaku Ryoho. 2006 Jun;33 Suppl 1:117-20.
• [4] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [5] [Thymidylate synthase gene promoter polymorphism in patients with advanced head and neck cancer treated by radio- and 5-fluorouracil chemotherapy]. Magy Onkol. 2006;50(1):33-7. Epub 2006 Apr 17.
• [6] 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.
• [7] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [8] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [9] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [10] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [11] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [12] 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.
• [13] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [14] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [15] Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
• [16] 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.
• [17] Psychotropic drug interactions with valproate. Clin Neuropharmacol. 2005 Mar-Apr;28(2):96-101.
• [18] The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
• [19] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [20] CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine delta-5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15.
• [21] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [22] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [23] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [24] Drug Interactions Flockhart Table
• [25] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [26] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [27] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [28] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [29] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
• [30] 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.
• [31] Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
• [32] 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.
• [33] 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.
• [34] Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
• [35] Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
• [36] CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
• [37] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [38] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [39] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [40] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [41] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.