General Information of Drug Combination (ID: DCH94DJ)

Drug Combination Name
Epirubicin Trifluridine
Indication
Disease Entry Status REF
Colon carcinoma Investigative [1]
Component Drugs Epirubicin   DMPDW6T Trifluridine   DMG2YBD
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KM12
Zero Interaction Potency (ZIP) Score: 12.78
Bliss Independence Score: 12.78
Loewe Additivity Score: 10.8
LHighest Single Agent (HSA) Score: 12.64

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Epirubicin
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [2]
Epirubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [5]
------------------------------------------------------------------------------------
Epirubicin Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [6]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
------------------------------------------------------------------------------------
Epirubicin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Epirubicin Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [9]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Increases Expression [9]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [9]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [10]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [11]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [12]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [13]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [14]
Retinoic acid receptor alpha (RARA) OT192V9V RARA_HUMAN Affects Mutagenesis [15]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Increases Phosphorylation [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [16]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [16]
Protein PML (PML) OT6SM2GD PML_HUMAN Affects Mutagenesis [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [17]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Expression [12]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [12]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Increases Phosphorylation [16]
FK506-binding protein-like (FKBPL) OTR9ND6K FKBPL_HUMAN Increases Expression [17]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Increases ADR [18]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Increases Response To Substance [19]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) OT9AGAIJ LHPP_HUMAN Increases ADR [18]
Alpha-protein kinase 1 (ALPK1) OTBW6SGD ALPK1_HUMAN Increases ADR [20]
Baculoviral IAP repeat-containing protein 6 (BIRC6) OTCQJAB0 BIRC6_HUMAN Decreases Response To Substance [21]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [22]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Affects Response To Substance [23]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [24]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Increases Response To Substance [25]
Little elongation complex subunit 1 (ICE1) OTOXTBUH ICE1_HUMAN Increases ADR [18]
Microcephalin (MCPH1) OTYT3TT5 MCPH1_HUMAN Increases ADR [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 30 DOT(s)
Indication(s) of Trifluridine
Disease Entry ICD 11 Status REF
Herpetic keratitis 1F00.10 Approved [3]
Virus infection 1A24-1D9Z Approved [4]
Colon cancer 2B90.Z Investigative [3]
Trifluridine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [26]
------------------------------------------------------------------------------------
Trifluridine Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [27]
Concentrative nucleoside transporter 1 (SLC28A1) DT0EQPW S28A1_HUMAN Substrate [28]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [28]
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [28]
------------------------------------------------------------------------------------
Trifluridine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [29]
------------------------------------------------------------------------------------
Trifluridine Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [30]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [31]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Increases Cleavage [32]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [32]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [32]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [32]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [33]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Glioma DCU3Y8P SF-539 Investigative [34]
Renal cell carcinoma DCEIUUR SN12C Investigative [34]
Lung adenocarcinoma DCBYC3V HOP-62 Investigative [35]
------------------------------------------------------------------------------------

References

1 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
2 New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31.
3 Trifluridine FDA Label
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8697).
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion. J Biomed Res. 2016 Mar;30(2):120-133.
7 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
8 Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab Dispos. 2006 Dec;34(12):2097-101.
9 Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells. Chem Biol Interact. 2015 Dec 5;242:13-23. doi: 10.1016/j.cbi.2015.08.023. Epub 2015 Sep 1.
10 Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 1999 Dec 1;59(23):5938-46.
11 Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity. Int J Clin Pharmacol Res. 1991;11(2):75-81.
12 7,3',4'-Trihydroxyisoflavone modulates multidrug resistance transporters and induces apoptosis via production of reactive oxygen species. Toxicology. 2012 Dec 16;302(2-3):221-32. doi: 10.1016/j.tox.2012.08.003. Epub 2012 Aug 15.
13 Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 2007 Sep;12(9):1124-33. doi: 10.1634/theoncologist.12-9-1124.
14 Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 2008 Dec;13(12):1296-305. doi: 10.1634/theoncologist.2008-0151. Epub 2008 Dec 5.
15 Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia. Blood. 2010 Jan 14;115(2):326-30. doi: 10.1182/blood-2009-07-235051. Epub 2009 Nov 2.
16 (-)-Gossypol enhances the anticancer activity of epirubicin via downregulating survivin in hepatocellular carcinoma. Chem Biol Interact. 2022 Sep 1;364:110060. doi: 10.1016/j.cbi.2022.110060. Epub 2022 Jul 22.
17 The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), pro-apoptotic protein (p21(WAF-1)) and anti-apoptotic protein (bcl-2) in breast cancer cells. Breast Cancer Res Treat. 2003 Aug;80(3):239-44. doi: 10.1023/A:1024995202135.
18 Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.
19 MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production. Ann Transl Med. 2019 May;7(9):200. doi: 10.21037/atm.2019.04.38.
20 Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
21 [Knock-down of apollon gene by antisense oligodeoxynucleotide inhibits the proliferation of Lovo cells and enhances chemo-sensitivity]. Yao Xue Xue Bao. 2011 Feb;46(2):138-45.
22 [Antisense oligonucleotide targeting survivin induces apoptosis of renal clear-cell carcinoma cells and enhances their sensitivity to epirubicin in vitro]. Zhonghua Zhong Liu Za Zhi. 2005 Aug;27(8):468-70.
23 Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity. Br J Cancer. 1998 Apr;77(7):1097-102. doi: 10.1038/bjc.1998.182.
24 S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
25 TSSC3 overexpression associates with growth inhibition, apoptosis induction and enhances chemotherapeutic effects in human osteosarcoma. Carcinogenesis. 2012 Jan;33(1):30-40. doi: 10.1093/carcin/bgr232. Epub 2011 Oct 21.
26 Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
27 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.
28 Lonsurf, INN-trifluridine/tipiracil.
29 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.
30 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.
31 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
32 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.
33 Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
34 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
35 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.