Details of the Drug Combination

General Information of Drug Combination (ID: DC8PVM1)

Drug Combination Name

Dactinomycin Busulfan

Indication

Disease Entry	Status	REF
Anaplastic large cell lymphoma	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: SR

Zero Interaction Potency (ZIP) Score: 2.16

Bliss Independence Score: 1.12

Loewe Additivity Score: 0.07

LHighest Single Agent (HSA) Score: 3.25

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 58 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response To Substance	[13]
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]
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]
Tumor protein p53-inducible protein 11 (TP53I11)	OTFPDYZU	P5I11_HUMAN	Decreases Expression	[14]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[15]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[16]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[17]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[17]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[18]
Proto-oncogene tyrosine-protein kinase ROS (ROS1)	OTDSKUGE	ROS1_HUMAN	Increases Expression	[17]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[19]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[20]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[17]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[17]
rRNA 2'-O-methyltransferase fibrillarin (FBL)	OTRODIE5	FBRL_HUMAN	Affects Localization	[21]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)	OTHJQ1DZ	RPB1_HUMAN	Decreases Phosphorylation	[22]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[23]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Expression	[17]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[24]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Decreases Expression	[17]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Decreases Expression	[17]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Increases Degradation	[25]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[26]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[27]
Hyaluronidase-1 (HYAL1)	OT2SJN0X	HYAL1_HUMAN	Increases ADR	[28]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Decreases Response To Substance	[29]
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⏷ Show the Full List of 58 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	[31]
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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	[32]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[33]
Glutathione S-transferase alpha-2 (GSTA2)	DEH49YS	GSTA2_HUMAN	Metabolism	[34]
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[35]
Microsomal glutathione S-transferase 2 (MGST2)	DE31KMQ	MGST2_HUMAN	Metabolism	[36]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[35]
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⏷ Show the Full List of 6 DME(s)

Busulfan Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[37]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Affects Expression	[38]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[39]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[39]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[40]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[40]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[30]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[30]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Activity	[41]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Activity	[41]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[41]
Signal transducer and activator of transcription 2 (STAT2)	OTO9G2RZ	STAT2_HUMAN	Decreases Expression	[30]
Pseudouridylate synthase 7 homolog (PUS7)	OTE5AQHJ	PUS7_HUMAN	Increases Expression	[42]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[43]
Rho GDP-dissociation inhibitor 1 (ARHGDIA)	OTEXWJDO	GDIR1_HUMAN	Affects Response To Substance	[44]
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⏷ Show the Full List of 15 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Lung adenocarcinoma	DCRWO02	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCJF5C7	NCI-H522	Investigative	[1]
Malignant melanoma	DCUZU8E	LOX IMVI	Investigative	[1]
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2	Dactinomycin FDA Label
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4	Busulfan FDA Label
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38	Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol. 2005 May;84(5):321-30. doi: 10.1007/s00277-004-0982-4. Epub 2004 Dec 4.
39	Antineoplastic agent busulfan regulates a network of genes related to coagulation and fibrinolysis. Eur J Clin Pharmacol. 2012 Jun;68(6):923-35. doi: 10.1007/s00228-011-1209-y.
40	Altered gene expression in busulfan-resistant human myeloid leukemia. Leuk Res. 2008 Nov;32(11):1684-97. doi: 10.1016/j.leukres.2008.01.016. Epub 2008 Mar 12.
41	Busulfan selectively induces cellular senescence but not apoptosis in WI38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen-activated protein kinase-dependent mechanism. J Pharmacol Exp Ther. 2006 Nov;319(2):551-60. doi: 10.1124/jpet.106.107771. Epub 2006 Aug 1.
42	CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
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44	Reduced expression of Rho guanine nucleotide dissociation inhibitor-alpha modulates the cytotoxic effect of busulfan in HEK293 cells. Anticancer Drugs. 2007 Mar;18(3):333-40. doi: 10.1097/CAD.0b013e328011fd7f.