Details of the Drug Combination

General Information of Drug Combination (ID: DC6CN26)

• Drug Combination Name: Epirubicin + Mechlorethamine
• Indication: Adult acute myeloid leukemia; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  Mechlorethamine (DM0CVXA): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HL-60(TB)
  Zero Interaction Potency (ZIP) Score: 28.94
  Bliss Independence Score: 29.14
  Loewe Additivity Score: 4.95
  LHighest Single Agent (HSA) Score: 9.64

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	[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]

Indication(s) of Mechlorethamine

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Lung cancer	2C25.0	Approved	[3]
Mycosis fungoides	2B01	Approved	[3]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[3]
Small lymphocytic lymphoma	2A82.0	Approved	[3]
T-cell lymphoma	2A90	Approved	[4]
Hodgkin lymphoma	2B30	Phase 3	[5]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]

Mechlorethamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Intercalator	[29]

Mechlorethamine Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[30]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Activity	[31]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[32]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Activity	[33]
Glutathione S-transferase A2 (GSTA2)	OTW7UB1H	GSTA2_HUMAN	Increases Expression	[34]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[32]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[35]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Activity	[33]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[32]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[32]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Stability	[33]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[33]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Expression	[36]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[37]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[35]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[35]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Decreases Expression	[38]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[39]
Transient receptor potential cation channel subfamily A member 1 (TRPA1)	OTRDIR5M	TRPA1_HUMAN	Increases Response To Substance	[40]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Clear cell renal cell carcinoma	DC9LSPA	TK-10	Investigative	[1]
Invasive ductal carcinoma	DC04J7X	HS 578T	Investigative	[41]
Adenocarcinoma	DCCP669	DU-145	Investigative	[42]
Adenocarcinoma	DCSRTVC	HCT-15	Investigative	[42]
Malignant melanoma	DCVQA2X	LOX IMVI	Investigative	[42]
Minimally invasive lung adenocarcinoma	DC33YRT	NCI-H322M	Investigative	[42]

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