Details of the Drug Combination

General Information of Drug Combination (ID: DCP5V6I)

Drug Combination Name

Dactinomycin Sorafenib

Indication

Disease Entry	Status	REF
Melanoma	Investigative	[1]

Component Drugs

Dactinomycin DM2YGNW

Sorafenib DMS8IFC

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

High-throughput Screening Result

Testing Cell Line: UACC-257

Zero Interaction Potency (ZIP) Score: 2.6

Bliss Independence Score: 4.71

Loewe Additivity Score: 4.9

LHighest Single Agent (HSA) Score: 2.24

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 Sorafenib

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[4]
Carcinoma	2A00-2F9Z	Approved	[4]
Clear cell renal carcinoma	N.A.	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Medullary thyroid gland carcinoma	N.A.	Approved	[4]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Renal cell carcinoma	2C90	Approved	[5]
Thyroid cancer	2D10	Approved	[4]
Hepatocellular carcinoma	2C12.02	Phase 3	[5]
Myelodysplastic syndrome	2A37	Phase 2	[5]

Sorafenib Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Modulator	[35]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Modulator	[35]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[36]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Modulator	[35]
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Sorafenib Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[37]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[38]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[39]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[40]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[41]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[40]
RalBP1-associated Eps domain-containing protein 2 (RALBP1)	DTYEM9B	REPS2_HUMAN	Substrate	[42]
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⏷ Show the Full List of 7 DTP(s)

Sorafenib Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[43]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[44]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[45]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[45]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[43]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[46]
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⏷ Show the Full List of 6 DME(s)

Sorafenib Interacts with 63 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Phosphorylation	[47]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[48]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Increases Expression	[48]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[49]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[50]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[50]
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PIK3C2A)	OTFBU4GD	P3C2A_HUMAN	Decreases Expression	[30]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[30]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Decreases Expression	[30]
Growth factor receptor-bound protein 2 (GRB2)	OTOP7LTE	GRB2_HUMAN	Decreases Expression	[30]
Interferon regulatory factor 5 (IRF5)	OT8SIIAP	IRF5_HUMAN	Increases Expression	[30]
Serine/threonine-protein kinase PLK3 (PLK3)	OT19CT2Z	PLK3_HUMAN	Increases Expression	[30]
Serine/threonine-protein kinase PLK2 (PLK2)	OTKMJXJ8	PLK2_HUMAN	Increases Expression	[30]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[48]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[51]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Decreases Expression	[52]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Decreases Expression	[31]
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Increases Ubiquitination	[53]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[54]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A)	OTYG179K	PR15A_HUMAN	Increases Expression	[32]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Increases Expression	[55]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Affects Localization	[52]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[56]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Activity	[47]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[54]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Phosphorylation	[57]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[58]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Decreases Phosphorylation	[52]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[59]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[31]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Activity	[60]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[48]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[61]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[62]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Decreases Phosphorylation	[63]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Decreases Phosphorylation	[63]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Phosphorylation	[63]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[64]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[65]
CCAAT/enhancer-binding protein delta (CEBPD)	OTNBIPMY	CEBPD_HUMAN	Increases Expression	[55]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Increases Response To Substance	[66]
Gasdermin-D (GSDMD)	OTH39BKI	GSDMD_HUMAN	Increases Expression	[67]
Sestrin-2 (SESN2)	OT889IXY	SESN2_HUMAN	Increases Expression	[68]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[69]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[70]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[52]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[71]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Decreases Expression	[72]
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Decreases Expression	[73]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Decreases Expression	[52]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[33]
Docking protein 1 (DOK1)	OTGVRLW6	DOK1_HUMAN	Decreases Phosphorylation	[64]
Serine/threonine-protein kinase PINK1, mitochondrial (PINK1)	OT50NR57	PINK1_HUMAN	Increases Expression	[53]
Eukaryotic translation initiation factor 2A (EIF2A)	OTWXELQP	EIF2A_HUMAN	Increases Phosphorylation	[32]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[74]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[27]
Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)	OT37FKH0	CYLD_HUMAN	Increases Expression	[75]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Affects Localization	[72]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Phosphorylation	[32]
E3 ubiquitin-protein ligase TRIM62 (TRIM62)	OT15YO6N	TRI62_HUMAN	Affects Response To Substance	[76]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Affects Response To Substance	[77]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Increases Response To Substance	[69]
Na(+)/citrate cotransporter (SLC13A5)	OTPH1TA7	S13A5_HUMAN	Decreases Response To Substance	[78]
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⏷ Show the Full List of 63 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Cutaneous melanoma	DCT1JEK	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCQIOTJ	OVCAR-8	Investigative	[1]
Lung adenocarcinoma	DC9XNQP	MDA-MB-231	Investigative	[1]
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