Details of the Drug Combination

General Information of Drug Combination (ID: DCP3ZUK)

• Drug Combination Name: Epirubicin + Gefitinib
• Indication: Carcinoma; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  Gefitinib (DM15F0X): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RXF 393
  Zero Interaction Potency (ZIP) Score: 6.93
  Bliss Independence Score: 9.85
  Loewe Additivity Score: 5.67
  LHighest Single Agent (HSA) Score: 13.01

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	[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 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
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]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[13]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[13]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[14]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[15]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[16]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[17]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[16]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[18]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[19]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[20]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[21]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[22]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[23]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[16]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[18]

Indication(s) of Gefitinib

Disease Entry	ICD 11	Status	REF
Colon adenocarcinoma	N.A.	Approved	[3]
Glioblastoma	2A00	Approved	[3]
Lung cancer	2C25.0	Approved	[3]
Non-small-cell lung cancer	2C25.Y	Approved	[3]
Rectal adenocarcinoma	2B92	Approved	[3]
Rectum mucinous adenocarcinoma	N.A.	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Head and neck cancer	2D42	Phase 3	[4]
Urethral cancer	2C93	Phase 2	[4]
Colon cancer	2B90.Z	Investigative	[3]
Colon mucinous adenocarcinoma	N.A.	Investigative	[3]

Gefitinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[29]

Gefitinib Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[30]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[31]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[31]

Gefitinib Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[32]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[33]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[32]

Gefitinib Interacts with 64 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases ADR	[34]
Sulfhydryl oxidase 1 (QSOX1)	OT4ZPK4P	QSOX1_HUMAN	Increases Expression	[35]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Decreases Expression	[35]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[35]
Fibroblast growth factor 6 (FGF6)	OTRJ679P	FGF6_HUMAN	Increases Expression	[35]
Ski oncogene (SKI)	OT4KJ8F6	SKI_HUMAN	Increases Expression	[35]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[35]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[35]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[35]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Increases Expression	[35]
Adenosine receptor A1 (ADORA1)	OTI7X39E	AA1R_HUMAN	Decreases Expression	[35]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[35]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Increases Expression	[35]
Epidermal growth factor receptor substrate 15 (EPS15)	OT7NPP8U	EPS15_HUMAN	Increases Expression	[35]
Neural retina-specific leucine zipper protein (NRL)	OT65MFKQ	NRL_HUMAN	Decreases Expression	[35]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2)	OT3JPRCQ	GBB2_HUMAN	Decreases Expression	[35]
Retinal guanylyl cyclase 1 (GUCY2D)	OT81UJI0	GUC2D_HUMAN	Decreases Expression	[35]
Cell growth regulator with RING finger domain protein 1 (CGRRF1)	OTLMNRCL	CGRF1_HUMAN	Increases Expression	[35]
Dual specificity protein phosphatase 9 (DUSP9)	OTZZWEQL	DUS9_HUMAN	Decreases Expression	[35]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[36]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[37]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[38]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[39]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[40]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Phosphorylation	[41]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA)	OTZE5Q7R	DOA_HUMAN	Affects Expression	[42]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Increases Secretion	[43]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[44]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[45]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Increases Secretion	[43]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[46]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[46]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[47]
HLA class I histocompatibility antigen, alpha chain F (HLA-F)	OT76CM19	HLAF_HUMAN	Affects Expression	[42]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[38]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Increases Expression	[40]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Decreases Phosphorylation	[25]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[47]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Response To Substance	[48]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[44]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[49]
Kelch-like ECH-associated protein 1 (KEAP1)	OTFHOD0C	KEAP1_HUMAN	Increases Expression	[50]
MHC class I polypeptide-related sequence B (MICB)	OTS2DVDW	MICB_HUMAN	Increases Expression	[51]
MHC class I polypeptide-related sequence A (MICA)	OTPEIEAR	MICA_HUMAN	Increases Expression	[51]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[42]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[39]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[52]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Decreases Response To Substance	[53]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Affects Response To Substance	[54]
Membrane-associated progesterone receptor component 1 (PGRMC1)	OTBE6WAC	PGRC1_HUMAN	Decreases Response To Substance	[55]
RNA-binding protein 7 (RBM7)	OTFIWTMF	RBM7_HUMAN	Affects Response To Substance	[56]
Cell death regulator Aven (AVEN)	OTGIN5YK	AVEN_HUMAN	Affects Response To Substance	[56]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Response To Substance	[57]
Phospholipase B-like 1 (PLBD1)	OTHYEB4W	PLBL1_HUMAN	Affects Response To Substance	[56]
Securin (PTTG1)	OTIMYS4W	PTTG1_HUMAN	Decreases Response To Substance	[44]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Affects Response To Substance	[56]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Affects Response To Substance	[28]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[58]
Ceramide transfer protein (CERT1)	OTNUCNHX	CERT_HUMAN	Affects Response To Substance	[56]
Dual specificity protein phosphatase 3 (DUSP3)	OTPJX9B4	DUS3_HUMAN	Affects Response To Substance	[56]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[59]
Pericentrin (PCNT)	OTW4Z65J	PCNT_HUMAN	Decreases Response To Substance	[55]
Coronin-1C (CORO1C)	OTXDF9T3	COR1C_HUMAN	Affects Response To Substance	[56]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Affects Response To Substance	[28]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCQEO3O	MOLT-4	Investigative	[60]
Anaplastic large cell lymphoma	DCH6SXM	SR	Investigative	[60]
Astrocytoma	DCL30CY	U251	Investigative	[60]
Childhood T acute lymphoblastic leukemia	DCH4EDP	CCRF-CEM	Investigative	[60]
Chronic myelogenous leukemia	DCY6J8K	K-562	Investigative	[60]
Clear cell renal cell carcinoma	DCBA2L2	A498	Investigative	[60]
Clear cell renal cell carcinoma	DCHDQX3	786-0	Investigative	[60]
Clear cell renal cell carcinoma	DCGOPVG	CAKI-1	Investigative	[60]
Glioblastoma	DC6Y91Y	SNB-75	Investigative	[60]
Glioma	DCGLSN4	SF-295	Investigative	[60]
Glioma	DCSE9H5	SF-539	Investigative	[60]
Renal cell carcinoma	DCOLS8Y	SN12C	Investigative	[60]
Breast adenocarcinoma	DCQRV6O	MDA-MB-468	Investigative	[1]
Carcinoma	DC3SX6G	MCF7	Investigative	[1]
Colon adenocarcinoma	DC0STK3	COLO 205	Investigative	[1]
Invasive ductal carcinoma	DCW54JG	T-47D	Investigative	[1]
Invasive ductal carcinoma	DC8O5KI	HS 578T	Investigative	[1]
Adenocarcinoma	DCA93RG	OVCAR3	Investigative	[61]
Adenocarcinoma	DCEAFVV	A549	Investigative	[61]
Adenocarcinoma	DC4AAYP	NCIH23	Investigative	[61]
Adenocarcinoma	DCSNWQ2	HCT116	Investigative	[61]
Amelanotic melanoma	DCV0B5O	MDA-MB-435	Investigative	[61]
Amelanotic melanoma	DC4YVAG	M14	Investigative	[61]
Cutaneous melanoma	DC9UFD0	SK-MEL-5	Investigative	[61]
Cutaneous melanoma	DCJXG4I	SK-MEL-28	Investigative	[61]
High grade ovarian serous adenocarcinoma	DCBDT3T	OVCAR-8	Investigative	[61]
Lung adenocarcinoma	DC76Y0N	HOP-62	Investigative	[61]
Malignant melanoma	DCCEQMI	LOX IMVI	Investigative	[61]
Malignant melanoma	DCBTSLH	UACC62	Investigative	[61]
Melanoma	DCDBPLA	UACC-257	Investigative	[61]
Melanoma	DCZVB4U	SK-MEL-2	Investigative	[61]
Mixed endometrioid and clear cell carcinoma	DC4FQG9	IGROV1	Investigative	[61]
Non-small cell lung carcinoma	DCTLOEV	HOP-92	Investigative	[61]
Ovarian serous cystadenocarcinoma	DCYBXDG	SK-OV-3	Investigative	[61]
Pleural epithelioid mesothelioma	DCBUDQ1	NCI-H226	Investigative	[61]

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