Details of the Drug Combination

General Information of Drug Combination (ID: DCIYZF2)

• Drug Combination Name: Dactinomycin + Imatinib
• Indication: Prostate carcinoma; Status: Investigative [1]
• Component Drugs:
  Dactinomycin (DM2YGNW): Small molecular drug
  Imatinib (DM7RJXL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: PC-3
  Zero Interaction Potency (ZIP) Score: 3.43
  Bliss Independence Score: 7.42
  Loewe Additivity Score: 4.39
  LHighest Single Agent (HSA) Score: 6.01

Molecular Interaction Atlas of This Drug Combination

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	[14]

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	[15]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[16]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[17]

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	[18]
Dihydropyrimidinase-related protein 4 (DPYSL4)	OT3SBS2S	DPYL4_HUMAN	Increases Expression	[11]
Integral membrane protein GPR137B (GPR137B)	OT1CINQQ	G137B_HUMAN	Increases Expression	[11]
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Increases Expression	[11]
Ras-related protein R-Ras (RRAS)	OTBBF28C	RRAS_HUMAN	Increases Expression	[11]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[11]
Stomatin (STOM)	OTC8R6EH	STOM_HUMAN	Increases Expression	[11]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Increases Expression	[11]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Increases Expression	[11]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[11]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Increases Expression	[11]
Galectin-7 (LGALS7)	OTMSVI7R	LEG7_HUMAN	Increases Expression	[11]
Large ribosomal subunit protein eL34 (RPL34)	OT0U9VMQ	RL34_HUMAN	Increases Expression	[11]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Expression	[11]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Increases Expression	[11]
Epithelial membrane protein 3 (EMP3)	OTODMJ1D	EMP3_HUMAN	Increases Expression	[11]
Protein ripply3 (RIPPLY3)	OT1HK35I	DSCR6_HUMAN	Increases Expression	[11]
Endonuclease III-like protein 1 (NTHL1)	OTPQXPT1	NTH_HUMAN	Decreases Expression	[11]
Kinesin-like protein KIF1A (KIF1A)	OT3JVEGV	KIF1A_HUMAN	Increases Expression	[11]
Protein AF1q (MLLT11)	OTG5RVHC	AF1Q_HUMAN	Increases Expression	[11]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[11]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Increases Expression	[11]
Immediate early response gene 5 protein (IER5)	OTJPTXMD	IER5_HUMAN	Increases Expression	[11]
Keratin, type II cytoskeletal 80 (KRT80)	OTAU54U3	K2C80_HUMAN	Increases Expression	[11]
All-trans-retinol 13,14-reductase (RETSAT)	OTC3AOPX	RETST_HUMAN	Increases Expression	[11]
Interleukin-27 receptor subunit alpha (IL27RA)	OTSQBAKI	I27RA_HUMAN	Increases Expression	[11]
Neuropilin and tolloid-like protein 2 (NETO2)	OT0YAMC0	NETO2_HUMAN	Increases Expression	[11]
Mitochondria-eating protein (SPATA18)	OTOEHTHU	MIEAP_HUMAN	Increases Expression	[11]
Phospholipase ABHD3 (ABHD3)	OTH8P977	ABHD3_HUMAN	Increases Expression	[11]
Homer protein homolog 3 (HOMER3)	OTQ6D9X1	HOME3_HUMAN	Increases Expression	[11]
BSD domain-containing protein 1 (BSDC1)	OT853CP9	BSDC1_HUMAN	Increases Expression	[11]
Stathmin-3 (STMN3)	OT20F289	STMN3_HUMAN	Increases Expression	[11]
Endothelial protein C receptor (PROCR)	OTRHED17	EPCR_HUMAN	Increases Expression	[11]
Fatty acid desaturase 3 (FADS3)	OT9RVXGE	FADS3_HUMAN	Increases Expression	[11]
Protein O-mannosyl-transferase 1 (POMT1)	OTGQSHL5	POMT1_HUMAN	Increases Expression	[11]
Tumor protein p53-inducible protein 11 (TP53I11)	OTFPDYZU	P5I11_HUMAN	Decreases Expression	[19]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[20]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[21]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[22]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[22]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[23]
Proto-oncogene tyrosine-protein kinase ROS (ROS1)	OTDSKUGE	ROS1_HUMAN	Increases Expression	[22]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[24]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[25]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[22]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[22]
rRNA 2'-O-methyltransferase fibrillarin (FBL)	OTRODIE5	FBRL_HUMAN	Affects Localization	[26]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)	OTHJQ1DZ	RPB1_HUMAN	Decreases Phosphorylation	[27]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[28]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Expression	[22]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[29]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Decreases Expression	[22]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Decreases Expression	[22]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Increases Degradation	[30]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[31]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[32]
Hyaluronidase-1 (HYAL1)	OT2SJN0X	HYAL1_HUMAN	Increases ADR	[33]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Decreases Response To Substance	[34]

Indication(s) of Imatinib

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[4]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	N.A.	Approved	[5]
Choroidal neovascularization	9B76	Approved	[5]
Chronic eosinophilic leukemia	N.A.	Approved	[5]
Chronic myelogenous leukaemia	2A20.0	Approved	[6]
Chronic myeloid leukaemia	2A20	Approved	[7]
Dermatofibrosarcoma protuberans	N.A.	Approved	[5]
Gastrointestinal stromal tumour	2B5B	Approved	[5]
Leukemia	N.A.	Approved	[5]
Malignant peripheral nerve sheath tumor	N.A.	Approved	[5]
Myeloproliferative neoplasm	2A20	Approved	[5]
Pulmonary hypertension	BB01	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[8]
Intestinal cancer	2C0Z	Phase 3	[6]
Lung cancer	2C25.0	Phase 2	[6]
Idiopathic hypereosinophilic syndrome	N.A.	Investigative	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[9]
Scleroderma	4A42	Investigative	[5]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[9]
Systemic mastocytosis	2A21.0	Investigative	[10]

Imatinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Mcl-1 messenger RNA (MCL-1 mRNA)	TTN6ORK	MCL1_HUMAN	.	[10]
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[38]
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[38]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[38]
HUMAN fusion protein Bcr-Abl (Bcr-Abl)	TTE63HY	BCR_HUMAN/ABL1_HUMAN	Inhibitor	[9]

Imatinib Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[39]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[40]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[41]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[42]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[43]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[41]

Imatinib Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[44]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[45]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[46]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[47]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[48]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[49]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[50]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[46]

Imatinib Interacts with 48 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Expression	[51]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[51]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Decreases Expression	[52]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Decreases Expression	[52]
Fructose-bisphosphate aldolase C (ALDOC)	OTEC13I5	ALDOC_HUMAN	Decreases Expression	[52]
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (PDHB)	OT2NHE5E	ODPB_HUMAN	Decreases Expression	[52]
Eukaryotic translation initiation factor 4B (EIF4B)	OTE8TXA8	IF4B_HUMAN	Decreases Expression	[52]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Decreases Expression	[52]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[52]
Hexokinase-4 (GCK)	OTR3Q0NN	HXK4_HUMAN	Decreases Expression	[52]
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)	OT83PT85	PP2AA_HUMAN	Increases Expression	[52]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[53]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[54]
Autophagy-related protein 13 (ATG13)	OTYMHNEJ	ATG13_HUMAN	Increases Phosphorylation	[35]
Keratin, type I cytoskeletal 14 (KRT14)	OTUVZ1DW	K1C14_HUMAN	Increases Expression	[55]
Heat shock protein beta-1 (HSPB1)	OTHFZ8ED	HSPB1_HUMAN	Increases Expression	[54]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Phosphorylation	[56]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[57]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[58]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[54]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[59]
Keratin, type II cytoskeletal 5 (KRT5)	OTVGI9HT	K2C5_HUMAN	Increases Expression	[55]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[60]
Transcription factor EB (TFEB)	OTJUJJQY	TFEB_HUMAN	Affects Localization	[35]
Insulin-like growth factor-binding protein 4 (IGFBP4)	OT2HZRBD	IBP4_HUMAN	Increases Expression	[54]
Interleukin-4 receptor subunit alpha (IL4R)	OTTXOTCW	IL4RA_HUMAN	Increases Expression	[54]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[56]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[56]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[61]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[62]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[35]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Expression	[54]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[61]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[63]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[64]
NGFI-A-binding protein 2 (NAB2)	OTG4BDF3	NAB2_HUMAN	Increases Expression	[54]
TRAF family member-associated NF-kappa-B activator (TANK)	OTZSGFIK	TANK_HUMAN	Increases Expression	[54]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[65]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[64]
Docking protein 1 (DOK1)	OTGVRLW6	DOK1_HUMAN	Decreases Phosphorylation	[66]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[35]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[32]
V-type proton ATPase subunit H (ATP6V1H)	OTX17GQ9	VATH_HUMAN	Increases Expression	[35]
LYR motif-containing protein 9 (LYRM9)	OT1MILTK	LYRM9_HUMAN	Affects Response To Substance	[67]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[68]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[69]
Tyrosine-protein kinase Lyn (LYN)	OTP686K2	LYN_HUMAN	Decreases Response To Substance	[62]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Increases Response To Substance	[58]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Colon carcinoma	DCWIKOG	KM12	Investigative	[70]
Adenocarcinoma	DCWVWLC	NCIH23	Investigative	[1]
Adenocarcinoma	DC4GWDK	A549	Investigative	[1]
Adenocarcinoma	DCW9TUY	HCT116	Investigative	[1]
Adenocarcinoma	DC69WGR	HT29	Investigative	[1]
Adult acute myeloid leukemia	DCQGJKJ	HL-60(TB)	Investigative	[1]
Amelanotic melanoma	DCJQIPX	M14	Investigative	[1]
Astrocytoma	DCKEV7X	U251	Investigative	[1]
Chronic myelogenous leukemia	DC8767S	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCQL3XU	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCSI9D3	TK-10	Investigative	[1]
Clear cell renal cell carcinoma	DCNDJBX	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DC7N931	CAKI-1	Investigative	[1]
Glioma	DCAPP5B	SF-539	Investigative	[1]
Glioma	DCEUHMM	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCQALY9	OVCAR-8	Investigative	[1]
Large cell lung carcinoma	DC89D8U	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC700AJ	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DC4P236	NCI-H522	Investigative	[1]
Malignant melanoma	DCMX5PS	LOX IMVI	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DC28TD9	IGROV1	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCYYWW7	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DCXFBXJ	ACHN	Investigative	[1]
Pleural epithelioid mesothelioma	DCIWOZM	NCI-H226	Investigative	[1]

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