General Information of Drug Combination (ID: DCFGXUI)

Drug Combination Name
Indazole derivative 5 Epirubicin
Indication
Disease Entry Status REF
Papillary renal cell carcinoma Investigative [1]
Component Drugs Indazole derivative 5   DMM1I8R Epirubicin   DMPDW6T
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: ACHN
Zero Interaction Potency (ZIP) Score: 2.86
Bliss Independence Score: 10.88
Loewe Additivity Score: 11.54
LHighest Single Agent (HSA) Score: 11.61

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indazole derivative 5 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ABL T315I mutant (ABL T315I) TTZJTWA ABL1_HUMAN Inhibitor [3]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I) TTIV39N BCR_HUMAN-ABL1_HUMAN Inhibitor [3]
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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 [4]
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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 [5]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [6]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [6]
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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 [7]
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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 [8]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Increases Expression [8]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [8]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [9]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [11]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [12]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [13]
Retinoic acid receptor alpha (RARA) OT192V9V RARA_HUMAN Affects Mutagenesis [14]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [8]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Increases Phosphorylation [15]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [15]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [15]
Protein PML (PML) OT6SM2GD PML_HUMAN Affects Mutagenesis [14]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [16]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Expression [11]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [11]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Increases Phosphorylation [15]
FK506-binding protein-like (FKBPL) OTR9ND6K FKBPL_HUMAN Increases Expression [16]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Increases ADR [17]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Increases Response To Substance [18]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) OT9AGAIJ LHPP_HUMAN Increases ADR [17]
Alpha-protein kinase 1 (ALPK1) OTBW6SGD ALPK1_HUMAN Increases ADR [19]
Baculoviral IAP repeat-containing protein 6 (BIRC6) OTCQJAB0 BIRC6_HUMAN Decreases Response To Substance [20]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [21]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Affects Response To Substance [22]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [23]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Increases Response To Substance [24]
Little elongation complex subunit 1 (ICE1) OTOXTBUH ICE1_HUMAN Increases ADR [17]
Microcephalin (MCPH1) OTYT3TT5 MCPH1_HUMAN Increases ADR [19]
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⏷ Show the Full List of 30 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCCOA1H 786-0 Investigative [1]
Clear cell renal cell carcinoma DC27J6K CAKI-1 Investigative [1]
Plasma cell myeloma DC8Y5KI RPMI-8226 Investigative [1]
Colon adenocarcinoma DC4LL4G COLO 205 Investigative [25]
Invasive ductal carcinoma DC0AQH1 BT-549 Investigative [25]
Adenocarcinoma DCYZ4RD DU-145 Investigative [26]
Adenocarcinoma DC53D9Y OVCAR3 Investigative [26]
Adenocarcinoma DCHLRW4 NCIH23 Investigative [26]
Cutaneous melanoma DCSFYKM SK-MEL-5 Investigative [26]
High grade ovarian serous adenocarcinoma DCXS0OC OVCAR-8 Investigative [26]
High grade ovarian serous adenocarcinoma DC7VFRF OVCAR-5 Investigative [26]
High grade ovarian serous adenocarcinoma DCB1CTU NCI\\/ADR-RES Investigative [26]
Lung adenocarcinoma DCM0G4M HOP-62 Investigative [26]
Melanoma DC86KGD UACC-257 Investigative [26]
Melanoma DCJB1QB SK-MEL-2 Investigative [26]
Minimally invasive lung adenocarcinoma DCB81B3 NCI-H322M Investigative [26]
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⏷ Show the Full List of 16 DrugCom(s)

References

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4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
5 Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion. J Biomed Res. 2016 Mar;30(2):120-133.
6 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.
7 Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab Dispos. 2006 Dec;34(12):2097-101.
8 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.
9 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.
10 Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity. Int J Clin Pharmacol Res. 1991;11(2):75-81.
11 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.
12 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.
13 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.
14 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.
15 (-)-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.
16 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.
17 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.
18 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.
19 Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
20 [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.
21 [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.
22 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.
23 S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
24 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.
25 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.
26 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.