Details of the Drug Combination

General Information of Drug Combination (ID: DC3SSV2)

• Drug Combination Name: Epirubicin + Lapatinib
• Indication: Childhood T acute lymphoblastic leukemia; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  Lapatinib (DM3BH1Y): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: CCRF-CEM
  Zero Interaction Potency (ZIP) Score: 1.03
  Bliss Independence Score: 6.35
  Loewe Additivity Score: 2.92
  LHighest Single Agent (HSA) Score: 2.48

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 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	[9]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[9]
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]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[13]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[14]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Mutagenesis	[15]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Increases Phosphorylation	[16]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[16]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[16]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[17]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[12]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[12]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Increases Phosphorylation	[16]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[17]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[18]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[19]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[18]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[20]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[21]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[22]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[23]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[24]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[25]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[18]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[20]

Indication(s) of Lapatinib

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[3]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[4]
Melanoma	2C30	Approved	[4]

Lapatinib Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[27]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[27]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[28]

Lapatinib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[29]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[30]

Lapatinib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[31]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[32]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[31]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[32]

Lapatinib Interacts with 36 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Activity	[33]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[34]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[35]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[35]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[35]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[35]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[36]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[33]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[37]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[38]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Decreases Expression	[39]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[39]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[39]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[37]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[40]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[41]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[42]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[33]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[37]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[37]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Activity	[33]
DNA replication licensing factor MCM7 (MCM7)	OT6FXC6K	MCM7_HUMAN	Decreases Expression	[37]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[39]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[33]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[39]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[39]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[38]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[43]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[44]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[45]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[46]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Metabolism	[39]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[39]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[46]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[45]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[45]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Clear cell renal cell carcinoma	DCDF8EJ	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DCOR3HF	CAKI-1	Investigative	[1]
Papillary renal cell carcinoma	DCN2TNA	ACHN	Investigative	[1]
Plasma cell myeloma	DCQ8QQ0	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DCGX5L0	SN12C	Investigative	[1]
Breast adenocarcinoma	DC32774	MDA-MB-468	Investigative	[47]
Invasive ductal carcinoma	DCU1YK4	HS 578T	Investigative	[47]
Invasive ductal carcinoma	DC0X8CP	BT-549	Investigative	[47]
Adenocarcinoma	DC88SAQ	HCT116	Investigative	[48]
Adenocarcinoma	DCXI5IP	HT29	Investigative	[48]
Amelanotic melanoma	DCEOB69	MDA-MB-435	Investigative	[48]
High grade ovarian serous adenocarcinoma	DCP1M5U	OVCAR-8	Investigative	[48]
Large cell lung carcinoma	DC6A6EP	NCI-H460	Investigative	[48]
Malignant melanoma	DCHED89	UACC62	Investigative	[48]
Melanoma	DC46TBK	UACC-257	Investigative	[48]
Mixed endometrioid and clear cell carcinoma	DCYD3FY	IGROV1	Investigative	[48]
Prostate carcinoma	DC097BP	PC-3	Investigative	[48]

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