Details of the Drug Combination

General Information of Drug Combination (ID: DC1V09B)

• Drug Combination Name: Crizotinib + Digitoxin
• Indication: Large cell lung carcinoma; Status: Investigative [1]
• Component Drugs:
  Crizotinib (DM4F29C): Small molecular drug
  Digitoxin (DMWVIGP): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCI-H460
  Zero Interaction Potency (ZIP) Score: 1.25
  Bliss Independence Score: 5.97
  Loewe Additivity Score: 2.65
  LHighest Single Agent (HSA) Score: 3.48

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	[7]
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Modulator	[7]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Modulator	[7]
HGF/Met signaling pathway (HGF/Met pathway)	TTKA5LP	NOUNIPROTAC	Inhibitor	[8]

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	[9]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[10]

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	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]

Crizotinib Interacts with 45 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[13]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Response To Substance	[5]
ALK tyrosine kinase receptor (ALK)	OTV3P4V8	ALK_HUMAN	Decreases Response To Substance	[14]
Prominin-1 (PROM1)	OTBHV8NX	PROM1_HUMAN	Decreases Expression	[4]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[4]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[4]
Cytidine deaminase (CDA)	OT3HXP6N	CDD_HUMAN	Decreases Expression	[4]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[15]
Acyl-CoA 6-desaturase (FADS2)	OTUX531P	FADS2_HUMAN	Increases Expression	[15]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[15]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Expression	[15]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[15]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[15]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Expression	[15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[15]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[15]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[15]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Decreases Activity	[15]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[5]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[5]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Secretion	[16]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[16]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Activity	[17]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[18]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[19]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[18]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[20]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[21]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[21]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[22]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[23]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1)	OTZRWTGA	IQGA1_HUMAN	Decreases Phosphorylation	[24]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[23]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[5]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[25]
Echinoderm microtubule-associated protein-like 4 (EML4)	OTJC45TA	EMAL4_HUMAN	Increases Mutagenesis	[21]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[26]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Decreases Response To Substance	[22]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[26]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Response To Substance	[14]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Decreases Response To Substance	[22]
Protransforming growth factor alpha (TGFA)	OTPD1LL9	TGFA_HUMAN	Decreases Response To Substance	[22]

Indication(s) of Digitoxin

Disease Entry	ICD 11	Status	REF
Arrhythmia	BC9Z	Approved	[3]
Congestive cardiac insufficiency	BD1Z	Approved	[3]
Heart failure	BD10-BD13	Approved	[3]

Digitoxin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/potassium-transporting ATPase (SPT ATPase)	TTQ38E9	AT1A1_HUMAN; AT1A2_HUMAN; AT1A3_HUMAN; AT1B1_HUMAN; AT1B2_HUMAN; AT1B3_HUMAN	Inhibitor	[27]

Digitoxin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[28]

Digitoxin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[29]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[30]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[31]

Digitoxin Interacts with 22 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[32]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Activity	[33]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Decreases Expression	[34]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[34]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Decreases Expression	[34]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[34]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Expression	[34]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Secretion	[35]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[34]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[36]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[36]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Phosphorylation	[35]
Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)	OT33XNZM	PTN6_HUMAN	Increases Expression	[36]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[34]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[34]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Decreases Expression	[34]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[34]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[36]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[34]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[36]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[34]
E3 SUMO-protein ligase PIAS3 (PIAS3)	OT3TWH9R	PIAS3_HUMAN	Increases Expression	[36]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DC2B108	SR	Investigative	[1]
Clear cell renal cell carcinoma	DCBLO11	TK-10	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC654JN	OVCAR-5	Investigative	[1]
Plasma cell myeloma	DCYAASH	RPMI-8226	Investigative	[1]

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