Details of the Drug Combination

General Information of Drug Combination (ID: DCEHYNT)

• Drug Combination Name: Crizotinib + Dactinomycin
• Indication: Colon adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Crizotinib (DM4F29C): Small molecular drug
  Dactinomycin (DM2YGNW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: COLO 205
  Zero Interaction Potency (ZIP) Score: 27.69
  Bliss Independence Score: 31.06
  Loewe Additivity Score: 28.23
  LHighest Single Agent (HSA) Score: 27.1

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Crizotinib

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[2]

Crizotinib Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Modulator	[8]
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Modulator	[8]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Modulator	[8]
HGF/Met signaling pathway (HGF/Met pathway)	TTKA5LP	NOUNIPROTAC	Inhibitor	[9]

Crizotinib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[11]

Crizotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]

Crizotinib Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[13]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Response To Substance	[6]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[5]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[5]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[14]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[14]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Expression	[14]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[14]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[14]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Decreases Activity	[14]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[6]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[6]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Secretion	[15]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[15]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Activity	[16]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[17]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[17]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[18]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[18]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1)	OTZRWTGA	IQGA1_HUMAN	Decreases Phosphorylation	[19]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[20]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[6]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[13]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Response To Substance	[21]

Indication(s) of Dactinomycin

Disease Entry	ICD 11	Status	REF
Adult kidney Wilms tumor	N.A.	Approved	[3]
Advanced cancer	2A00-2F9Z	Approved	[3]
Beckwith-Wiedemann syndrome	N.A.	Approved	[3]
Childhood kidney Wilms tumor	N.A.	Approved	[3]
Gestational trophoblastic neoplasia	2F33-2F76	Approved	[3]
Hamartoma	N.A.	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Wilms tumor	N.A.	Approved	[3]

Dactinomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[25]

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	[26]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[28]

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	[29]
Dihydropyrimidinase-related protein 4 (DPYSL4)	OT3SBS2S	DPYL4_HUMAN	Increases Expression	[22]
Integral membrane protein GPR137B (GPR137B)	OT1CINQQ	G137B_HUMAN	Increases Expression	[22]
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Increases Expression	[22]
Ras-related protein R-Ras (RRAS)	OTBBF28C	RRAS_HUMAN	Increases Expression	[22]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[22]
Stomatin (STOM)	OTC8R6EH	STOM_HUMAN	Increases Expression	[22]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Increases Expression	[22]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Increases Expression	[22]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[22]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Increases Expression	[22]
Galectin-7 (LGALS7)	OTMSVI7R	LEG7_HUMAN	Increases Expression	[22]
Large ribosomal subunit protein eL34 (RPL34)	OT0U9VMQ	RL34_HUMAN	Increases Expression	[22]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Expression	[22]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Increases Expression	[22]
Epithelial membrane protein 3 (EMP3)	OTODMJ1D	EMP3_HUMAN	Increases Expression	[22]
Protein ripply3 (RIPPLY3)	OT1HK35I	DSCR6_HUMAN	Increases Expression	[22]
Endonuclease III-like protein 1 (NTHL1)	OTPQXPT1	NTH_HUMAN	Decreases Expression	[22]
Kinesin-like protein KIF1A (KIF1A)	OT3JVEGV	KIF1A_HUMAN	Increases Expression	[22]
Protein AF1q (MLLT11)	OTG5RVHC	AF1Q_HUMAN	Increases Expression	[22]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[22]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Increases Expression	[22]
Immediate early response gene 5 protein (IER5)	OTJPTXMD	IER5_HUMAN	Increases Expression	[22]
Keratin, type II cytoskeletal 80 (KRT80)	OTAU54U3	K2C80_HUMAN	Increases Expression	[22]
All-trans-retinol 13,14-reductase (RETSAT)	OTC3AOPX	RETST_HUMAN	Increases Expression	[22]
Interleukin-27 receptor subunit alpha (IL27RA)	OTSQBAKI	I27RA_HUMAN	Increases Expression	[22]
Neuropilin and tolloid-like protein 2 (NETO2)	OT0YAMC0	NETO2_HUMAN	Increases Expression	[22]
Mitochondria-eating protein (SPATA18)	OTOEHTHU	MIEAP_HUMAN	Increases Expression	[22]
Phospholipase ABHD3 (ABHD3)	OTH8P977	ABHD3_HUMAN	Increases Expression	[22]
Homer protein homolog 3 (HOMER3)	OTQ6D9X1	HOME3_HUMAN	Increases Expression	[22]
BSD domain-containing protein 1 (BSDC1)	OT853CP9	BSDC1_HUMAN	Increases Expression	[22]
Stathmin-3 (STMN3)	OT20F289	STMN3_HUMAN	Increases Expression	[22]
Endothelial protein C receptor (PROCR)	OTRHED17	EPCR_HUMAN	Increases Expression	[22]
Fatty acid desaturase 3 (FADS3)	OT9RVXGE	FADS3_HUMAN	Increases Expression	[22]
Protein O-mannosyl-transferase 1 (POMT1)	OTGQSHL5	POMT1_HUMAN	Increases Expression	[22]
Tumor protein p53-inducible protein 11 (TP53I11)	OTFPDYZU	P5I11_HUMAN	Decreases Expression	[30]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[31]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[32]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[33]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[33]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[34]
Proto-oncogene tyrosine-protein kinase ROS (ROS1)	OTDSKUGE	ROS1_HUMAN	Increases Expression	[33]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[35]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[36]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[33]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[33]
rRNA 2'-O-methyltransferase fibrillarin (FBL)	OTRODIE5	FBRL_HUMAN	Affects Localization	[37]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)	OTHJQ1DZ	RPB1_HUMAN	Decreases Phosphorylation	[38]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[39]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Expression	[33]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[40]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Decreases Expression	[33]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Decreases Expression	[33]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Increases Degradation	[41]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[42]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[43]
Hyaluronidase-1 (HYAL1)	OT2SJN0X	HYAL1_HUMAN	Increases ADR	[44]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Decreases Response To Substance	[45]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCGBFJV	DU-145	Investigative	[46]
Adenocarcinoma	DCYXQP3	OVCAR3	Investigative	[46]
Adenocarcinoma	DCSY44I	NCIH23	Investigative	[46]
Adenocarcinoma	DCBJROT	A549	Investigative	[46]
Adenocarcinoma	DCICKID	HCT-15	Investigative	[46]
Adenocarcinoma	DCV4ED5	HCC-2998	Investigative	[46]
Adenocarcinoma	DC4CHLC	HCT116	Investigative	[46]
Adenocarcinoma	DC72SVJ	HT29	Investigative	[46]
Adenocarcinoma	DCTM2VR	SW-620	Investigative	[46]
Adult acute myeloid leukemia	DCT7N31	HL-60(TB)	Investigative	[46]
Adult T acute lymphoblastic leukemia	DCJTW71	MOLT-4	Investigative	[46]
Amelanotic melanoma	DCP08BD	MDA-MB-435	Investigative	[46]
Amelanotic melanoma	DCDWN5V	M14	Investigative	[46]
Anaplastic large cell lymphoma	DCTIF62	SR	Investigative	[46]
Astrocytoma	DCJ3QW9	U251	Investigative	[46]
Astrocytoma	DC9UNYK	SNB-19	Investigative	[46]
Childhood T acute lymphoblastic leukemia	DCOAPGG	CCRF-CEM	Investigative	[46]
Chronic myelogenous leukemia	DCTZMB9	K-562	Investigative	[46]
Clear cell renal cell carcinoma	DCXXGZ0	A498	Investigative	[46]
Clear cell renal cell carcinoma	DCHCD94	786-0	Investigative	[46]
Clear cell renal cell carcinoma	DC6JQU9	TK-10	Investigative	[46]
Clear cell renal cell carcinoma	DCX161V	CAKI-1	Investigative	[46]
Cutaneous melanoma	DCYYU14	SK-MEL-28	Investigative	[46]
Cutaneous melanoma	DCA5OAG	SK-MEL-5	Investigative	[46]
Glioblastoma	DCLK35J	SNB-75	Investigative	[46]
Glioma	DCQ8ZM2	SF-295	Investigative	[46]
Glioma	DC3LUSM	SF-268	Investigative	[46]
Glioma	DCYHDXY	SF-539	Investigative	[46]
High grade ovarian serous adenocarcinoma	DCC3GF7	OVCAR-8	Investigative	[46]
High grade ovarian serous adenocarcinoma	DCPFL6Q	OVCAR-5	Investigative	[46]
Large cell lung carcinoma	DCRVMVX	NCI-H460	Investigative	[46]
Lung adenocarcinoma	DCQZ8QM	HOP-62	Investigative	[46]
Lung adenocarcinoma	DCP5VHA	EKVX	Investigative	[46]
Lung adenocarcinoma	DCWCJKU	MDA-MB-231	Investigative	[46]
Lung adenocarcinoma	DCSOSPE	NCI-H522	Investigative	[46]
Malignant melanoma	DCUCW5T	LOX IMVI	Investigative	[46]
Malignant melanoma	DCH6KZT	UACC62	Investigative	[46]
Melanoma	DCO3NSG	MALME-3M	Investigative	[46]
Melanoma	DCFMXX9	UACC-257	Investigative	[46]
Minimally invasive lung adenocarcinoma	DCV2I0W	NCI-H322M	Investigative	[46]
Mixed endometrioid and clear cell carcinoma	DCC6S8H	IGROV1	Investigative	[46]
Non-small cell lung carcinoma	DC5A4QV	HOP-92	Investigative	[46]
Ovarian serous cystadenocarcinoma	DCC20BU	SK-OV-3	Investigative	[46]
Papillary renal cell carcinoma	DCAFED8	ACHN	Investigative	[46]
Plasma cell myeloma	DCJYOZB	RPMI-8226	Investigative	[46]
Pleural epithelioid mesothelioma	DCQHMBK	NCI-H226	Investigative	[46]
Prostate carcinoma	DC3AYBY	PC-3	Investigative	[46]
Renal cell carcinoma	DCTCI7X	SN12C	Investigative	[46]
Breast adenocarcinoma	DCAWYGN	MDA-MB-468	Investigative	[1]
Carcinoma	DC2UWOA	RXF 393	Investigative	[1]
Carcinoma	DCSUD37	MCF7	Investigative	[1]
Colon carcinoma	DCHIZD5	KM12	Investigative	[1]
Invasive ductal carcinoma	DCM6MKZ	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DCQWVQ7	T-47D	Investigative	[1]
Invasive ductal carcinoma	DCPJVP9	BT-549	Investigative	[1]

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