Details of the Drug Combination

General Information of Drug Combination (ID: DCTNT0E)

• Drug Combination Name: Epirubicin + DFN-15
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  DFN-15 (DM3BF9B): N.A.
• High-throughput Screening Result:
  Testing Cell Line: BT-549
  Zero Interaction Potency (ZIP) Score: 4.71
  Bliss Independence Score: 8.92
  Loewe Additivity Score: 6.08
  LHighest Single Agent (HSA) Score: 6.29

Molecular Interaction Atlas of This Drug Combination

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]

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]

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]

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	[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]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[12]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[12]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[13]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[14]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[15]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[16]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[15]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[17]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[18]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[19]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[20]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[21]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[22]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[15]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[17]

Indication(s) of DFN-15

Disease Entry	ICD 11	Status	REF
Migraine	8A80	Phase 3	[3]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DC8FKKH	MOLT-4	Investigative	[23]
Anaplastic large cell lymphoma	DCT94J0	SR	Investigative	[23]
Childhood T acute lymphoblastic leukemia	DCFY8CM	CCRF-CEM	Investigative	[23]
Chronic myelogenous leukemia	DCR5W5M	K-562	Investigative	[23]
Clear cell renal cell carcinoma	DC2VOX3	A498	Investigative	[23]
Clear cell renal cell carcinoma	DC130R4	TK-10	Investigative	[23]
Glioma	DC6E1RE	SF-268	Investigative	[23]
Papillary renal cell carcinoma	DCHUA1O	ACHN	Investigative	[23]
Renal cell carcinoma	DCWSUIY	UO-31	Investigative	[23]
Breast adenocarcinoma	DC4JW8M	MDA-MB-468	Investigative	[1]
Carcinoma	DCMCWRL	RXF 393	Investigative	[1]
Colon adenocarcinoma	DCUMOMN	COLO 205	Investigative	[1]
Invasive ductal carcinoma	DCW9DPF	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DCID271	T-47D	Investigative	[1]
Adenocarcinoma	DC21SFI	OVCAR3	Investigative	[24]
Amelanotic melanoma	DCNM0WO	MDA-MB-435	Investigative	[24]
Amelanotic melanoma	DCPW6SL	M14	Investigative	[24]
Cutaneous melanoma	DC0A5D5	SK-MEL-28	Investigative	[24]
Cutaneous melanoma	DC6V772	SK-MEL-5	Investigative	[24]
Lung adenocarcinoma	DC3UVSE	HOP-62	Investigative	[24]
Lung adenocarcinoma	DCOOZ90	MDA-MB-231	Investigative	[24]
Lung adenocarcinoma	DCJYP37	NCI-H522	Investigative	[24]
Malignant melanoma	DCYPERS	UACC62	Investigative	[24]
Melanoma	DC7U70M	MALME-3M	Investigative	[24]
Melanoma	DCO5JLC	UACC-257	Investigative	[24]
Mixed endometrioid and clear cell carcinoma	DCINDT9	IGROV1	Investigative	[24]
Non-small cell lung carcinoma	DCEGT94	HOP-92	Investigative	[24]
Ovarian serous cystadenocarcinoma	DCCIA4X	SK-OV-3	Investigative	[24]
Pleural epithelioid mesothelioma	DCRBIWD	NCI-H226	Investigative	[24]

References

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• [2] New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] 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.
• [12] (-)-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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
• [18] [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.
• [19] [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.
• [20] 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.
• [21] S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
• [22] 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.
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• [24] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976