Details of the Drug Combination

General Information of Drug Combination (ID: DCUZU8E)

Drug Combination Name

Dactinomycin Busulfan

Indication

Disease Entry	Status	REF
Malignant melanoma	Investigative	[1]

Component Drugs

Dactinomycin DM2YGNW

Busulfan DMXYJ9C

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

High-throughput Screening Result

Testing Cell Line: LOX IMVI

Zero Interaction Potency (ZIP) Score: 2.4

Bliss Independence Score: 5.29

Loewe Additivity Score: 0.21

LHighest Single Agent (HSA) Score: 4.11

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Dactinomycin

Disease Entry	ICD 11	Status	REF
Adult kidney Wilms tumor	N.A.	Approved	[2]
Advanced cancer	2A00-2F9Z	Approved	[2]
Beckwith-Wiedemann syndrome	N.A.	Approved	[2]
Childhood kidney Wilms tumor	N.A.	Approved	[2]
Gestational trophoblastic neoplasia	2F33-2F76	Approved	[2]
Hamartoma	N.A.	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Wilms tumor	N.A.	Approved	[2]

Dactinomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[9]
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Dactinomycin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[10]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]
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Dactinomycin Interacts with 85 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[13]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response To Substance	[14]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Increases Expression	[6]
Dihydropyrimidinase-related protein 4 (DPYSL4)	OT3SBS2S	DPYL4_HUMAN	Increases Expression	[6]
Integral membrane protein GPR137B (GPR137B)	OT1CINQQ	G137B_HUMAN	Increases Expression	[6]
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Increases Expression	[6]
Ras-related protein R-Ras (RRAS)	OTBBF28C	RRAS_HUMAN	Increases Expression	[6]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[6]
Stomatin (STOM)	OTC8R6EH	STOM_HUMAN	Increases Expression	[6]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Increases Expression	[6]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Increases Expression	[6]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[6]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Increases Expression	[6]
Galectin-7 (LGALS7)	OTMSVI7R	LEG7_HUMAN	Increases Expression	[6]
Large ribosomal subunit protein eL34 (RPL34)	OT0U9VMQ	RL34_HUMAN	Increases Expression	[6]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Expression	[6]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Increases Expression	[6]
Epithelial membrane protein 3 (EMP3)	OTODMJ1D	EMP3_HUMAN	Increases Expression	[6]
Protein ripply3 (RIPPLY3)	OT1HK35I	DSCR6_HUMAN	Increases Expression	[6]
Endonuclease III-like protein 1 (NTHL1)	OTPQXPT1	NTH_HUMAN	Decreases Expression	[6]
Antigen peptide transporter 1 (TAP1)	OTJL27PW	TAP1_HUMAN	Increases Expression	[6]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[6]
Kinesin-like protein KIF1A (KIF1A)	OT3JVEGV	KIF1A_HUMAN	Increases Expression	[6]
Protein AF1q (MLLT11)	OTG5RVHC	AF1Q_HUMAN	Increases Expression	[6]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[6]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Increases Expression	[6]
Immediate early response gene 5 protein (IER5)	OTJPTXMD	IER5_HUMAN	Increases Expression	[6]
Keratin, type II cytoskeletal 80 (KRT80)	OTAU54U3	K2C80_HUMAN	Increases Expression	[6]
All-trans-retinol 13,14-reductase (RETSAT)	OTC3AOPX	RETST_HUMAN	Increases Expression	[6]
Interleukin-27 receptor subunit alpha (IL27RA)	OTSQBAKI	I27RA_HUMAN	Increases Expression	[6]
Neuropilin and tolloid-like protein 2 (NETO2)	OT0YAMC0	NETO2_HUMAN	Increases Expression	[6]
Mitochondria-eating protein (SPATA18)	OTOEHTHU	MIEAP_HUMAN	Increases Expression	[6]
Phospholipase ABHD3 (ABHD3)	OTH8P977	ABHD3_HUMAN	Increases Expression	[6]
Homer protein homolog 3 (HOMER3)	OTQ6D9X1	HOME3_HUMAN	Increases Expression	[6]
BSD domain-containing protein 1 (BSDC1)	OT853CP9	BSDC1_HUMAN	Increases Expression	[6]
Stathmin-3 (STMN3)	OT20F289	STMN3_HUMAN	Increases Expression	[6]
Endothelial protein C receptor (PROCR)	OTRHED17	EPCR_HUMAN	Increases Expression	[6]
Fatty acid desaturase 3 (FADS3)	OT9RVXGE	FADS3_HUMAN	Increases Expression	[6]
Protein O-mannosyl-transferase 1 (POMT1)	OTGQSHL5	POMT1_HUMAN	Increases Expression	[6]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[15]
Tumor protein p53-inducible protein 11 (TP53I11)	OTFPDYZU	P5I11_HUMAN	Decreases Expression	[16]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[17]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[18]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[19]
Prominin-1 (PROM1)	OTBHV8NX	PROM1_HUMAN	Decreases Expression	[20]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[19]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Decreases Expression	[21]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Response To Substance	[22]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[23]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Increases Expression	[19]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[24]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[25]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[23]
Proto-oncogene tyrosine-protein kinase ROS (ROS1)	OTDSKUGE	ROS1_HUMAN	Increases Expression	[19]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Decreases Expression	[26]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Expression	[27]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[28]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[29]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[30]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[31]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[20]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Decreases Expression	[19]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[19]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[19]
rRNA 2'-O-methyltransferase fibrillarin (FBL)	OTRODIE5	FBRL_HUMAN	Affects Localization	[32]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)	OTHJQ1DZ	RPB1_HUMAN	Decreases Phosphorylation	[33]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[34]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Increases Expression	[19]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[19]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Cleavage	[35]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Expression	[19]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Decreases Expression	[19]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[36]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[37]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[38]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Decreases Expression	[19]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Decreases Expression	[19]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Increases Degradation	[39]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[19]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[29]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Decreases Expression	[26]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[40]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[20]
Hyaluronidase-1 (HYAL1)	OT2SJN0X	HYAL1_HUMAN	Increases ADR	[41]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Decreases Response To Substance	[42]
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⏷ Show the Full List of 85 DOT(s)

Indication(s) of Busulfan

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[4]
Hematologic disease	3C0Z	Approved	[4]
Immunodeficiency	4A00-4A85	Approved	[4]
Leukemia	N.A.	Approved	[4]
Myeloproliferative syndrome	2A22	Approved	[5]
Systemic lupus erythematosus	4A40.0	Approved	[4]
Systemic sclerosis	4A42	Approved	[4]
Neuroblastoma	2D11.2	Investigative	[4]
Retinoblastoma	2D02.2	Investigative	[4]

Busulfan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[44]
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Busulfan Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[45]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[46]
Glutathione S-transferase alpha-2 (GSTA2)	DEH49YS	GSTA2_HUMAN	Metabolism	[47]
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[48]
Microsomal glutathione S-transferase 2 (MGST2)	DE31KMQ	MGST2_HUMAN	Metabolism	[49]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[48]
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⏷ Show the Full List of 6 DME(s)

Busulfan Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Affects Abundance	[50]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Abundance	[50]
Microsomal glutathione S-transferase 2 (MGST2)	OT4UGTDO	MGST2_HUMAN	Decreases Response To Substance	[49]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Response To Substance	[51]
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[52]
Inhibin beta A chain (INHBA)	OTSP64PQ	INHBA_HUMAN	Increases Expression	[52]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[52]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Affects Expression	[53]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[54]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[54]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[43]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[55]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[54]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[54]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[56]
Tissue factor pathway inhibitor (TFPI)	OTA0FX16	TFPI1_HUMAN	Decreases Expression	[54]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[56]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[43]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[43]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Activity	[57]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Activity	[57]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[43]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Affects Expression	[43]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[57]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Affects Expression	[43]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[58]
Signal transducer and activator of transcription 2 (STAT2)	OTO9G2RZ	STAT2_HUMAN	Decreases Expression	[43]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[56]
Metal regulatory transcription factor 1 (MTF1)	OTJWVLLF	MTF1_HUMAN	Decreases Expression	[43]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[43]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[43]
Pseudouridylate synthase 7 homolog (PUS7)	OTE5AQHJ	PUS7_HUMAN	Increases Expression	[59]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[60]
Rho GDP-dissociation inhibitor 1 (ARHGDIA)	OTEXWJDO	GDIR1_HUMAN	Affects Response To Substance	[58]
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⏷ Show the Full List of 34 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DC8PVM1	SR	Investigative	[1]
Lung adenocarcinoma	DCRWO02	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCJF5C7	NCI-H522	Investigative	[1]
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