General Information of Drug Combination (ID: DC4H0ZR)

Drug Combination Name
Raloxifene Epirubicin
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Raloxifene   DMDKF3M Epirubicin   DMPDW6T
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: A549
Zero Interaction Potency (ZIP) Score: 0.48
Bliss Independence Score: 3.65
Loewe Additivity Score: 1.65
LHighest Single Agent (HSA) Score: 1.07

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Raloxifene
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Approved [2]
Raloxifene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Modulator [4]
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Raloxifene Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
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Raloxifene Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [8]
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Indication(s) of Epirubicin
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [3]
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 [9]
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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 [10]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [11]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
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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 [12]
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Epirubicin Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [13]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [14]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [15]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [17]
Protein PML (PML) OT6SM2GD PML_HUMAN Affects Mutagenesis [18]
FK506-binding protein-like (FKBPL) OTR9ND6K FKBPL_HUMAN Increases Expression [19]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Increases ADR [20]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Increases Response To Substance [21]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) OT9AGAIJ LHPP_HUMAN Increases ADR [20]
Alpha-protein kinase 1 (ALPK1) OTBW6SGD ALPK1_HUMAN Increases ADR [22]
Baculoviral IAP repeat-containing protein 6 (BIRC6) OTCQJAB0 BIRC6_HUMAN Decreases Response To Substance [23]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [24]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Affects Response To Substance [25]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [26]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Increases Response To Substance [27]
Little elongation complex subunit 1 (ICE1) OTOXTBUH ICE1_HUMAN Increases ADR [20]
Microcephalin (MCPH1) OTYT3TT5 MCPH1_HUMAN Increases ADR [22]
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⏷ Show the Full List of 19 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCISJ8Q MOLT-4 Investigative [28]
Astrocytoma DCD3WUE U251 Investigative [28]
Astrocytoma DC8H8MP SNB-19 Investigative [28]
Childhood T acute lymphoblastic leukemia DC19IIG CCRF-CEM Investigative [28]
Chronic myelogenous leukemia DCIXE37 K-562 Investigative [28]
Clear cell renal cell carcinoma DCABI0R TK-10 Investigative [28]
Clear cell renal cell carcinoma DC2GHEO 786-0 Investigative [28]
Clear cell renal cell carcinoma DCNLRXG CAKI-1 Investigative [28]
Glioma DCCUWXC SF-268 Investigative [28]
Papillary renal cell carcinoma DC8RR3G ACHN Investigative [28]
Plasma cell myeloma DCM3MWU RPMI-8226 Investigative [28]
Carcinoma DC6ISHY RXF 393 Investigative [29]
Colon adenocarcinoma DC5TED2 COLO 205 Investigative [29]
Invasive ductal carcinoma DC78E56 HS 578T Investigative [29]
Invasive ductal carcinoma DCVG7XP T-47D Investigative [29]
Invasive ductal carcinoma DCCBAP2 BT-549 Investigative [29]
Adenocarcinoma DCU5FHC DU-145 Investigative [1]
Adenocarcinoma DCTB825 OVCAR3 Investigative [1]
Adenocarcinoma DCU07RQ NCIH23 Investigative [1]
Adenocarcinoma DCLHA8D HCT-15 Investigative [1]
Adenocarcinoma DCVFRMR SW-620 Investigative [1]
Amelanotic melanoma DC26C0L M14 Investigative [1]
Cutaneous melanoma DC9987P SK-MEL-28 Investigative [1]
Cutaneous melanoma DCFCVX6 SK-MEL-5 Investigative [1]
High grade ovarian serous adenocarcinoma DC7OLWZ OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCV3HX5 OVCAR-5 Investigative [1]
High grade ovarian serous adenocarcinoma DCS0D8A NCI\\/ADR-RES Investigative [1]
Large cell lung carcinoma DCCVQCF NCI-H460 Investigative [1]
Lung adenocarcinoma DCGQE06 EKVX Investigative [1]
Malignant melanoma DCMMPZF UACC62 Investigative [1]
Melanoma DC36LNN SK-MEL-2 Investigative [1]
Melanoma DC11CQ8 MALME-3M Investigative [1]
Melanoma DCL9J1V UACC-257 Investigative [1]
Mixed endometrioid and clear cell carcinoma DC721N3 IGROV1 Investigative [1]
Non-small cell lung carcinoma DCPMI71 HOP-92 Investigative [1]
Ovarian serous cystadenocarcinoma DCDNCIA SK-OV-3 Investigative [1]
Pleural epithelioid mesothelioma DC6YN7E NCI-H226 Investigative [1]
Prostate carcinoma DCVBALQ PC-3 Investigative [1]
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⏷ Show the Full List of 38 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31.
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. (Target id: 620).
5 Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308.
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7 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.
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9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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12 Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab Dispos. 2006 Dec;34(12):2097-101.
13 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.
14 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.
15 Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity. Int J Clin Pharmacol Res. 1991;11(2):75-81.
16 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.
17 (-)-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.
18 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.
19 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.
20 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.
21 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.
22 Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
23 [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.
24 [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.
25 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.
26 S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
27 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.
28 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
29 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165