Details of the Drug Combination

General Information of Drug Combination (ID: DC8EG5B)

• Drug Combination Name: Vandetanib + Plicamycin
• Indication: Carcinoma; Status: Investigative [1]
• Component Drugs:
  Vandetanib (DMRICNP): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RXF 393
  Zero Interaction Potency (ZIP) Score: 1.94
  Bliss Independence Score: 7.27
  Loewe Additivity Score: 8.13
  LHighest Single Agent (HSA) Score: 8.24

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vandetanib

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[2]

Vandetanib Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[6]
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Inhibitor	[6]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[6]

Vandetanib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[8]

Vandetanib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

Vandetanib Interacts with 22 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Increases Expression	[10]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[10]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[10]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L)	OTJKOMXE	BNI3L_HUMAN	Increases Expression	[10]
Protein FAM13A (FAM13A)	OTZ6GN0Q	FA13A_HUMAN	Increases Expression	[10]
Phosphoglycerate kinase 1 (PGK1)	OT6V1ICH	PGK1_HUMAN	Increases Expression	[10]
Calbindin (CALB1)	OTM7IXDG	CALB1_HUMAN	Increases Expression	[10]
Prothymosin alpha (PTMA)	OT2W4T1M	PTMA_HUMAN	Decreases Expression	[10]
Trypsin-2 (PRSS2)	OTOMVUWL	TRY2_HUMAN	Increases Expression	[10]
Gamma-enolase (ENO2)	OTRODL0T	ENOG_HUMAN	Increases Expression	[10]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Increases Expression	[10]
Histone H1.2 (H1-2)	OT0AVI4M	H12_HUMAN	Increases Expression	[10]
DNA mismatch repair protein Msh3 (MSH3)	OTD3YPVL	MSH3_HUMAN	Decreases Expression	[10]
Pro-adrenomedullin (ADM)	OT7T0TA4	ADML_HUMAN	Increases Expression	[10]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[11]
Collagen alpha-3(IV) chain (COL4A3)	OT6SB8X5	CO4A3_HUMAN	Increases Expression	[10]
Solute carrier family 2, facilitated glucose transporter member 14 (SLC2A14)	OTBFIOVY	GTR14_HUMAN	Increases Expression	[10]
Protein NDRG1 (NDRG1)	OTVO66BO	NDRG1_HUMAN	Increases Expression	[10]
TSC22 domain family protein 3 (TSC22D3)	OT03UM03	T22D3_HUMAN	Increases Expression	[10]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[12]
Hypoxia-inducible lipid droplet-associated protein (HILPDA)	OTEID3ZM	HLPDA_HUMAN	Increases Expression	[10]
Insulin-induced gene 2 protein (INSIG2)	OTX4VY51	INSI2_HUMAN	Increases Expression	[10]

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	[14]

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	[15]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[16]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[17]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[18]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[13]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[17]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[19]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[20]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DCMXU67	MDA-MB-468	Investigative	[1]
Carcinoma	DC4MX92	MCF7	Investigative	[1]
Colon adenocarcinoma	DCFG64T	COLO 205	Investigative	[1]
Colon carcinoma	DC1ZUME	KM12	Investigative	[1]
Invasive ductal carcinoma	DCXL1JX	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DCSVKD2	BT-549	Investigative	[1]
Invasive ductal carcinoma	DC075PN	T-47D	Investigative	[1]
Adenocarcinoma	DC2KTUU	OVCAR3	Investigative	[21]
Adenocarcinoma	DC1RR2M	HCC-2998	Investigative	[21]
Adenocarcinoma	DC2MQOI	SW-620	Investigative	[21]
Adult acute myeloid leukemia	DC0N9PP	HL-60(TB)	Investigative	[21]
Adult T acute lymphoblastic leukemia	DCYRQMC	MOLT-4	Investigative	[21]
Amelanotic melanoma	DC4A7V8	M14	Investigative	[21]
Amelanotic melanoma	DCMGISY	MDA-MB-435	Investigative	[21]
Anaplastic large cell lymphoma	DC4V16Y	SR	Investigative	[21]
Astrocytoma	DCRV7HJ	U251	Investigative	[21]
Astrocytoma	DC16JX9	SNB-19	Investigative	[21]
Childhood T acute lymphoblastic leukemia	DCTSJJX	CCRF-CEM	Investigative	[21]
Chronic myelogenous leukemia	DCU3OPO	K-562	Investigative	[21]
Clear cell renal cell carcinoma	DCXJP64	786-0	Investigative	[21]
Clear cell renal cell carcinoma	DCX5T9P	A498	Investigative	[21]
Clear cell renal cell carcinoma	DC1CX8P	TK-10	Investigative	[21]
Clear cell renal cell carcinoma	DCESLPW	CAKI-1	Investigative	[21]
Cutaneous melanoma	DC9749A	SK-MEL-28	Investigative	[21]
Cutaneous melanoma	DCM0HO4	SK-MEL-5	Investigative	[21]
Glioblastoma	DC5ITWK	SNB-75	Investigative	[21]
Glioma	DCMCFDA	SF-268	Investigative	[21]
Glioma	DC7VTDP	SF-295	Investigative	[21]
Glioma	DCL880I	SF-539	Investigative	[21]
High grade ovarian serous adenocarcinoma	DCWYWBU	OVCAR-4	Investigative	[21]
High grade ovarian serous adenocarcinoma	DCLGCPM	OVCAR-8	Investigative	[21]
High grade ovarian serous adenocarcinoma	DC3CCR0	OVCAR-5	Investigative	[21]
Large cell lung carcinoma	DC8T1LI	NCI-H460	Investigative	[21]
Malignant melanoma	DCMN2WW	UACC62	Investigative	[21]
Melanoma	DCYWALF	MALME-3M	Investigative	[21]
Melanoma	DCPUVQO	SK-MEL-2	Investigative	[21]
Melanoma	DCSJF9W	UACC-257	Investigative	[21]
Minimally invasive lung adenocarcinoma	DCF0Q6H	NCI-H322M	Investigative	[21]
Ovarian serous cystadenocarcinoma	DCHXIWX	SK-OV-3	Investigative	[21]
Papillary renal cell carcinoma	DCIQWLL	ACHN	Investigative	[21]
Plasma cell myeloma	DCFBSJ0	RPMI-8226	Investigative	[21]
Pleural epithelioid mesothelioma	DCAQR6T	NCI-H226	Investigative	[21]
Renal cell carcinoma	DCFH1B7	UO-31	Investigative	[21]

References

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• [15] SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
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• [18] The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
• [19] Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
• [20] Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
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