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

General Information of Drug (ID: DMG2YBD)

Drug Name
Trifluridine Drug Info
Synonyms
Fluridine; TFDU; TRIFLUOROTHYMIDINE; Trifluoridine; Trifluoromethyldeoxyuridine; Trifluridina; Trifluridinum; Virophta; Viroptic; Trifluorothymine deoxyriboside; CF3dUrd; F3DThd; F3T; F3TDR; HS-0007; Trifluridina [INN-Spanish]; Trifluridine [USAN:INN]; Trifluridinum [INN-Latin]; Viroptic (TN); Trifluridine (USP/INN);Viroptic, Trifluorothymidine, Trifluridine; Alpha,alpha,alpha-Trifluorothymidine; 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione; 2'-Deoxy-5-(trifluoromethyl)uridine; 2'-Deoxy-5-trifluoromethyluridine; 5-(Trifluoromethyl)-2'-deoxyuridine; 5-(Trifluoromethyl)deoxyuridine; 5-Trifluoro-2'-deoxythymidine; 5-Trifluoromethyl-2'-deoxyuridine; 5-Trifluoromethyl-2-deoxyuridine; 5-Trifluorothymidine
Indication
Disease Entry ICD 11 Status REF
Herpetic keratitis 1F00.10 Approved [1]
Virus infection 1A24-1D9Z Approved [2]
Colon cancer 2B90.Z Investigative [1]
Therapeutic Class
Antiviral Agents
Cross-matching ID
PubChem CID
6256
ChEBI ID
CHEMBL1129
CAS Number
CAS 70-00-8
TTD Drug ID
DMG2YBD
VARIDT Drug ID
DR00096
INTEDE Drug ID
DR1643

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DME
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Discontinued Drug(s)
Investigative Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Candida Thymidylate synthase (Candi TMP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [9]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [10]
Pemetrexed DMMX2E6 Central nervous system lymphoma 2B33.5 Approved [11]
Capecitabine DMTS85L Adenocarcinoma 2D40 Approved [12]
Raltitrexed DMT9K8G Rectal adenocarcinoma 2B92 Approved [13]
Floxuridine DM04LR2 Colorectal cancer 2B91.Z Approved [14]
Flucytosine DM13VTW Cryptococcal meningitis Approved [15]
Nolatrexed DMOF0CA Solid tumour/cancer 2A00-2F9Z Phase 3 [16]
Plevitrexed (R)-isomer DMTL39C Gastric adenocarcinoma 2B72 Phase 2 [17]
Plevitrexed DM7Y60I Gastric adenocarcinoma 2B72 Phase 2 [17]
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Drug(s) Transported By Organic anion transporter 1 (SLC22A6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Amoxicillin DMUYNEI Acute otitis media AB00 Approved [18]
Methotrexate DM2TEOL Anterior urethra cancer Approved [19]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [20]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [21]
Aciclovir DMYLOVR Genital herpes 1A94 Approved [21]
Ganciclovir DM1MBYQ Cytomegalovirus infection 1D82 Approved [21]
Cefazolin DMPDYFR Bacteremia 1A73 Approved [22]
Olmesartan medoxomil DMWBHRY High blood pressure BA00 Approved [23]
Zalcitabine DMH7MUV Human immunodeficiency virus infection 1C62 Approved [24]
FLUORESCEIN DMQTFAO Ocular disease 1F00.1Z Approved [25]
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Drug(s) Transported By Concentrative nucleoside transporter 1 (SLC28A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cytarabine DMZD5QR Acute lymphoblastic leukaemia 2A85 Approved [26]
Gemcitabine DMSE3I7 Anterior urethra cancer Approved [27]
Uridine DMQTREB Depression 6A70-6A7Z Approved [28]
Drug(s) Transported By Equilibrative nucleoside transporter 1 (SLC29A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [29]
Mercaptopurine DMTM2IK Acute lymphoblastic leukaemia 2A85 Approved [30]
Cytarabine DMZD5QR Acute lymphoblastic leukaemia 2A85 Approved [26]
Entecavir DM7VTQO Hepatitis B virus infection 1E51.0 Approved [31]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [32]
Clofarabine DMCVJ86 Acute lymphoblastic leukaemia 2A85 Approved [33]
Adenosine DMM2NSK Paroxysmal supraventricular tachycardia BC81.Z Approved [34]
Tecadenoson DM9T6MS Atrial fibrillation BC81.3 Discontinued in Phase 3 [35]
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Drug(s) Transported By Equilibrative nucleoside transporter 2 (SLC29A2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Mercaptopurine DMTM2IK Acute lymphoblastic leukaemia 2A85 Approved [30]
Cytarabine DMZD5QR Acute lymphoblastic leukaemia 2A85 Approved [26]
Entecavir DM7VTQO Hepatitis B virus infection 1E51.0 Approved [31]
Clofarabine DMCVJ86 Acute lymphoblastic leukaemia 2A85 Approved [33]
Drug(s) Metabolized By Thymidine phosphorylase (TYMP)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [36]
Capecitabine DMTS85L Adenocarcinoma 2D40 Approved [37]
Floxuridine DM04LR2 Colorectal cancer 2B91.Z Approved [38]
Deoxythymidine DMR90HY Discovery agent N.A. Investigative [39]
Drug(s) Affected By Nuclear receptor subfamily 1 group I member 2 (NR1I2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Verapamil DMA7PEW Angina pectoris BA40 Approved [7]
Vidarabine DM0N85H Hepatosplenic T-cell lymphoma Approved [7]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [40]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [41]
Secobarbital DM14RF5 Epilepsy 8A60-8A68 Approved [42]
Etidronic acid DM1XHYJ Bone Paget disease Approved [7]
Tiaprofenic acid DM23D7J Osteoarthritis FA00-FA05 Approved [7]
Bromperidol DM24XYQ Schizophrenia 6A20 Approved [7]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [43]
Deoxycholic acid DM3GYAL Subcutaneous fat disorder EF02 Approved [44]
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Drug(s) Affected By Poly polymerase 1 (PARP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [45]
Gefitinib DM15F0X Colon adenocarcinoma Approved [46]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [47]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [48]
Citalopram DM2G9AE Acute coronary syndrome BA41 Approved [49]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [50]
Imipramine DM2NUH3 Depression 6A70-6A7Z Approved [49]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [51]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [52]
Methotrexate DM2TEOL Anterior urethra cancer Approved [53]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [4]
Concentrative nucleoside transporter 1 (SLC28A1) DT0EQPW S28A1_HUMAN Substrate [4]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [4]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Thymidine phosphorylase (TYMP) Main DME DE4HCYL TYPH_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Gene/Protein Processing [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [8]

References

1 Trifluridine FDA Label
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3 Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
4 Lonsurf, INN-trifluridine/tipiracil.
5 Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9.
6 Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9.
7 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
8 Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int J Cancer. 2010 May 15;126(10):2457-68. doi: 10.1002/ijc.24943.
9 The efficacy of the combination therapy of 5-fluorouracil, cisplatin and leucovorin for hepatocellular carcinoma and its predictable factors. Cancer Chemother Pharmacol. 2004 Apr;53(4):296-304.
10 Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer. 2003 Feb 20;103(5):587-99.
11 Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
12 UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
13 DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
14 Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol. 1999 Aug;127(8):1777-86.
15 Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
16 A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. Br J Cancer. 1999 Feb;79(5-6):915-20.
17 Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors. Biochemistry. 2007 Mar 13;46(10):2823-30.
18 The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002 Jan;30(1):13-9.
19 Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9.
20 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
21 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
22 Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004 Jan;21(1):61-7.
23 Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
24 Interaction of zalcitabine with human organic anion transporter 1. Pharmazie. 2006 May;61(5):491-2.
25 Apical expression or expression in a non polarized cell of hOAT1 inverses regulation by epidermal growth factor (EGF) as compared to basolateral hOAT1. Cell Physiol Biochem. 2004;14(3):177-86.
26 FLT3 is implicated in cytarabine transport by human equilibrative nucleoside transporter 1 in pediatric acute leukemia. Oncotarget. 2016 Aug 2;7(31):49786-49799.
27 Pancreatic Cancer Chemoresistance to Gemcitabine. Cancers (Basel). 2017 Nov 16;9(11).
28 Electrophysiological recordings of CNT1 (SLC28A1) activity on Nanions SURFE2R N1.
29 Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer. Anticancer Res. 2007 Jul-Aug;27(4B):2241-9.
30 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA2040)
31 Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
32 Effects of dipyridamole coadministration on the pharmacokinetics of ribavirin in healthy volunteers. Drug Metab Pharmacokinet. 2013;28(5):406-10.
33 Cytarabine-resistant leukemia cells are moderately sensitive to clofarabine in vitro. Anticancer Res. 2014 Apr;34(4):1657-62.
34 Nitric oxide reduces adenosine transporter ENT1 gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes. J Cell Physiol. 2006 Aug;208(2):451-60.
35 Transport of A1 adenosine receptor agonist tecadenoson by human and mouse nucleoside transporters: evidence for blood-brain barrier transport by murine equilibrative nucleoside transporter 1 mENT1. Drug Metab Dispos. 2013 Apr;41(4):916-22.
36 5-Fluorouracil pharmacogenomics: still rocking after all these years? Pharmacogenomics. 2011 Feb;12(2):251-65.
37 Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
38 Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm. 2008 Sep-Oct;5(5):717-27.
39 Thymidine catabolism as a metabolic strategy for cancer survival. Cell Rep. 2017 May 16;19(7):1313-1321.
40 Induction of PXR-mediated metabolism by beta-carotene. Biochim Biophys Acta. 2005 May 30;1740(2):162-9. doi: 10.1016/j.bbadis.2004.11.013. Epub 2004 Dec 8.
41 Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol. 2005 Dec 1;209(2):123-33. doi: 10.1016/j.taap.2005.03.015.
42 Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
43 Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
44 Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.
45 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
46 Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
47 Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
48 Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
49 The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
50 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.
51 Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
52 Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
53 Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.