General Information of Drug Combination (ID: DCM5QGF)

Drug Combination Name
Epirubicin Plicamycin
Indication
Disease Entry Status REF
Plasma cell myeloma Investigative [1]
Component Drugs Epirubicin   DMPDW6T Plicamycin   DM7C8YV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: RPMI-8226
Zero Interaction Potency (ZIP) Score: 37.77
Bliss Independence Score: 33.09
Loewe Additivity Score: 26.99
LHighest Single Agent (HSA) Score: 25.62

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 [6]
------------------------------------------------------------------------------------
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 [7]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [8]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
------------------------------------------------------------------------------------
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 [9]
------------------------------------------------------------------------------------
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 [10]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Increases Expression [10]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [10]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [11]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [13]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [14]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [15]
Retinoic acid receptor alpha (RARA) OT192V9V RARA_HUMAN Affects Mutagenesis [16]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [10]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Increases Phosphorylation [17]
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 [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [18]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Expression [13]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [13]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Increases Phosphorylation [17]
FK506-binding protein-like (FKBPL) OTR9ND6K FKBPL_HUMAN Increases Expression [18]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Increases ADR [19]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Increases Response To Substance [20]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) OT9AGAIJ LHPP_HUMAN Increases ADR [19]
Alpha-protein kinase 1 (ALPK1) OTBW6SGD ALPK1_HUMAN Increases ADR [21]
Baculoviral IAP repeat-containing protein 6 (BIRC6) OTCQJAB0 BIRC6_HUMAN Decreases Response To Substance [22]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [23]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Affects Response To Substance [24]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [25]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Increases Response To Substance [26]
Little elongation complex subunit 1 (ICE1) OTOXTBUH ICE1_HUMAN Increases ADR [19]
Microcephalin (MCPH1) OTYT3TT5 MCPH1_HUMAN Increases ADR [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 30 DOT(s)
Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [3]
Testicular cancer 2C80 Approved [3]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [4]
Lung cancer 2C25.0 Investigative [5]
Ovarian cancer 2C73 Investigative [5]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [28]
------------------------------------------------------------------------------------
Plicamycin Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [29]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [30]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [30]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [30]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [31]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [31]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [32]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [27]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [33]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [34]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [35]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [27]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [36]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [33]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [37]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [38]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCXJMTQ MOLT-4 Investigative [1]
Anaplastic large cell lymphoma DC1XM5T SR Investigative [1]
Astrocytoma DCOOD4P SNB-19 Investigative [1]
Childhood T acute lymphoblastic leukemia DC6GGW1 CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCTJQJ3 K-562 Investigative [1]
Clear cell renal cell carcinoma DCGJFPH TK-10 Investigative [1]
Clear cell renal cell carcinoma DCZXV64 786-0 Investigative [1]
Clear cell renal cell carcinoma DCWDMWY A498 Investigative [1]
Clear cell renal cell carcinoma DCQ8BYR CAKI-1 Investigative [1]
Glioblastoma DC3NJFE SNB-75 Investigative [1]
Glioma DC4HPZP SF-268 Investigative [1]
Glioma DC5STQ8 SF-295 Investigative [1]
Papillary renal cell carcinoma DCZXQ2Y ACHN Investigative [1]
Renal cell carcinoma DCHWXFQ SN12C Investigative [1]
Renal cell carcinoma DC4WAR4 UO-31 Investigative [1]
Carcinoma DC3MMPT RXF 393 Investigative [39]
Carcinoma DCFHZG2 MCF7 Investigative [39]
Colon adenocarcinoma DCS4SOO COLO 205 Investigative [39]
Invasive ductal carcinoma DCV7W7E BT-549 Investigative [39]
Invasive ductal carcinoma DC2H8LI T-47D Investigative [39]
Invasive ductal carcinoma DCBXL01 HS 578T Investigative [39]
Adenocarcinoma DCYYID2 DU-145 Investigative [40]
Adenocarcinoma DCUJ7XR HT29 Investigative [40]
Adenocarcinoma DCYEWYY HCT-15 Investigative [40]
Amelanotic melanoma DCHEJ7P M14 Investigative [40]
Amelanotic melanoma DCU9PTZ MDA-MB-435 Investigative [40]
High grade ovarian serous adenocarcinoma DCC58MZ OVCAR-5 Investigative [40]
High grade ovarian serous adenocarcinoma DCQGSCU OVCAR-8 Investigative [40]
Large cell lung carcinoma DCN5R9V NCI-H460 Investigative [40]
Lung adenocarcinoma DC8GQNX HOP-62 Investigative [40]
Lung adenocarcinoma DCMSPFZ EKVX Investigative [40]
Lung adenocarcinoma DCK73UI NCI-H522 Investigative [40]
Malignant melanoma DC1OVDB UACC62 Investigative [40]
Malignant melanoma DCXRK7Y LOX IMVI Investigative [40]
Melanoma DCOER6L MALME-3M Investigative [40]
Melanoma DCHXUCR UACC-257 Investigative [40]
Minimally invasive lung adenocarcinoma DCRYPZD NCI-H322M Investigative [40]
Ovarian serous cystadenocarcinoma DC8X13Q SK-OV-3 Investigative [40]
Pleural epithelioid mesothelioma DCIIJJU NCI-H226 Investigative [40]
------------------------------------------------------------------------------------
⏷ Show the Full List of 39 DrugCom(s)

References

1 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.
2 New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 8394).
5 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion. J Biomed Res. 2016 Mar;30(2):120-133.
8 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.
9 Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab Dispos. 2006 Dec;34(12):2097-101.
10 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.
11 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.
12 Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity. Int J Clin Pharmacol Res. 1991;11(2):75-81.
13 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.
14 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.
15 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.
16 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.
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 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.
19 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.
20 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.
21 Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
22 [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.
23 [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.
24 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.
25 S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
26 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.
27 The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
28 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
29 SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
30 Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):138-48.
31 Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
32 Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
33 Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
34 Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. Lung. 2004;182(4):251-64. doi: 10.1007/s00408-004-2507-2.
35 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
36 CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
37 Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
38 Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
39 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.
40 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.