Details of the Drug Combination

General Information of Drug Combination (ID: DCQDL57)

• Drug Combination Name: Epirubicin + Letrozole
• Indication: Amelanotic melanoma; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  Letrozole (DMH07Y3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: M14
  Zero Interaction Potency (ZIP) Score: 2.22
  Bliss Independence Score: 8.35
  Loewe Additivity Score: 5.53
  LHighest Single Agent (HSA) Score: 4.96

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 Letrozole

Disease Entry	ICD 11	Status	REF
Estrogen-receptor positive breast cancer	N.A.	Approved	[3]
Hormonally-responsive breast cancer	2C60-2C65	Approved	[4]

Letrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[26]

Letrozole Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[27]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[28]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[29]

Letrozole Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[30]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[31]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Oxidation	[31]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[32]
Dickkopf-related protein 1 (DKK1)	OTRDLUSP	DKK1_HUMAN	Increases Expression	[33]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[34]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[34]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[35]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[33]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[36]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[37]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[37]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[38]
Leukemia inhibitory factor receptor (LIFR)	OT36W9O5	LIFR_HUMAN	Increases Expression	[33]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[35]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[37]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Activity	[39]
Fibroblast growth factor 22 (FGF22)	OTVIX6J0	FGF22_HUMAN	Increases Expression	[33]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCTRRTW	MOLT-4	Investigative	[40]
Anaplastic large cell lymphoma	DCXHEYT	SR	Investigative	[40]
Astrocytoma	DCGWXTI	SNB-19	Investigative	[40]
Clear cell renal cell carcinoma	DCVMN6Z	A498	Investigative	[40]
Glioma	DC44MPA	SF-268	Investigative	[40]
Renal cell carcinoma	DCVXTNE	SN12C	Investigative	[40]
Invasive ductal carcinoma	DCPYJ3T	BT-549	Investigative	[41]
Invasive ductal carcinoma	DC6U98C	HS 578T	Investigative	[41]
Amelanotic melanoma	DC6X7KU	MDA-MB-435	Investigative	[1]
Cutaneous melanoma	DCDHQCI	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCKH9C1	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC1XUKC	NCI\\/ADR-RES	Investigative	[1]
Melanoma	DCUWSXO	UACC-257	Investigative	[1]
Non-small cell lung carcinoma	DCWT86F	HOP-92	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCT3PPQ	SK-OV-3	Investigative	[1]
Pleural epithelioid mesothelioma	DC9YIGW	NCI-H226	Investigative	[1]

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