Details of the Drug Combination

General Information of Drug Combination (ID: DC1J8QM)

• Drug Combination Name: Crizotinib + Plicamycin
• Indication: Clear cell renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Crizotinib (DM4F29C): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: A498
  Zero Interaction Potency (ZIP) Score: 9.09
  Bliss Independence Score: 14.37
  Loewe Additivity Score: 13.88
  LHighest Single Agent (HSA) Score: 14.54

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	[3]
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Modulator	[3]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Modulator	[3]
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	[7]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[6]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[6]
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	[7]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[7]
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	[7]
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 Plicamycin

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[3]
Testicular cancer	2C80	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[4]
Lung cancer	2C25.0	Investigative	[5]
Ovarian cancer	2C73	Investigative	[5]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[23]

Plicamycin Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[24]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[25]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[26]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[27]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[22]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[26]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[28]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[29]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCXM143	DU-145	Investigative	[1]
Adenocarcinoma	DCKV3NM	OVCAR3	Investigative	[1]
Adenocarcinoma	DCPVFAH	HCT116	Investigative	[1]
Adenocarcinoma	DC55L55	HCC-2998	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCHPEDV	MOLT-4	Investigative	[1]
Amelanotic melanoma	DCOS0DF	MDA-MB-435	Investigative	[1]
Amelanotic melanoma	DCR0DAO	M14	Investigative	[1]
Anaplastic large cell lymphoma	DC9WV79	SR	Investigative	[1]
Astrocytoma	DCUHW44	U251	Investigative	[1]
Astrocytoma	DCT9OYY	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCG16DE	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCHQMJ6	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DC8E6WP	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DCJUB8I	TK-10	Investigative	[1]
Clear cell renal cell carcinoma	DC8HPW1	CAKI-1	Investigative	[1]
Cutaneous melanoma	DCIZ3GN	SK-MEL-28	Investigative	[1]
Cutaneous melanoma	DC1Y6RV	SK-MEL-5	Investigative	[1]
Glioblastoma	DCVPUYT	SNB-75	Investigative	[1]
Glioma	DC90BL6	SF-295	Investigative	[1]
Glioma	DC8VIJI	SF-268	Investigative	[1]
Glioma	DCSUDOW	SF-539	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC55RQG	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCWC2L6	OVCAR-5	Investigative	[1]
Large cell lung carcinoma	DCNOP70	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCTCN6L	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCIUPRB	EKVX	Investigative	[1]
Malignant melanoma	DCLJEUD	UACC62	Investigative	[1]
Melanoma	DCLS8EE	MALME-3M	Investigative	[1]
Melanoma	DCZUU50	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC9MK6R	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCEX8AR	IGROV1	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC3MRU4	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DC85ME0	ACHN	Investigative	[1]
Plasma cell myeloma	DC04PH7	RPMI-8226	Investigative	[1]
Pleural epithelioid mesothelioma	DCWMO3L	NCI-H226	Investigative	[1]
Renal cell carcinoma	DCJ3GO6	UO-31	Investigative	[1]
Renal cell carcinoma	DC7JS5M	SN12C	Investigative	[1]
Breast adenocarcinoma	DCNAOT2	MDA-MB-468	Investigative	[30]
Carcinoma	DC8E6GH	RXF 393	Investigative	[30]
Carcinoma	DCIGX4H	MCF7	Investigative	[30]
Colon adenocarcinoma	DCZ73OY	COLO 205	Investigative	[30]
Colon carcinoma	DCVCNVM	KM12	Investigative	[30]
Invasive ductal carcinoma	DCQ3VUC	HS 578T	Investigative	[30]
Invasive ductal carcinoma	DCTE2BZ	BT-549	Investigative	[30]
Invasive ductal carcinoma	DCBOZI7	T-47D	Investigative	[30]

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