Details of the Drug Combination

General Information of Drug Combination (ID: DC5FXKO)

• Drug Combination Name: Vandetanib + Romidepsin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Vandetanib (DMRICNP): Small molecular drug
  Romidepsin (DMT5GNL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: K-562
  Zero Interaction Potency (ZIP) Score: 0.17
  Bliss Independence Score: 2.59
  Loewe Additivity Score: 1.2
  LHighest Single Agent (HSA) Score: 3.29

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 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proto-oncogene tyrosine-protein kinase receptor Ret (RET)	OTLU040A	RET_HUMAN	Decreases Phosphorylation	[10]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Increases Expression	[11]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[11]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[11]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L)	OTJKOMXE	BNI3L_HUMAN	Increases Expression	[11]
Protein FAM13A (FAM13A)	OTZ6GN0Q	FA13A_HUMAN	Increases Expression	[11]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Activity	[12]
Phosphoglycerate kinase 1 (PGK1)	OT6V1ICH	PGK1_HUMAN	Increases Expression	[11]
Calbindin (CALB1)	OTM7IXDG	CALB1_HUMAN	Increases Expression	[11]
Prothymosin alpha (PTMA)	OT2W4T1M	PTMA_HUMAN	Decreases Expression	[11]
Trypsin-2 (PRSS2)	OTOMVUWL	TRY2_HUMAN	Increases Expression	[11]
Insulin-like growth factor-binding protein 1 (IGFBP1)	OT6UQV2K	IBP1_HUMAN	Increases Expression	[11]
Gamma-enolase (ENO2)	OTRODL0T	ENOG_HUMAN	Increases Expression	[11]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Increases Expression	[11]
Mucin-1 (MUC1)	OTHQI7IY	MUC1_HUMAN	Increases Expression	[11]
Histone H1.2 (H1-2)	OT0AVI4M	H12_HUMAN	Increases Expression	[11]
Insulin-like growth factor-binding protein 3 (IGFBP3)	OTIX63TX	IBP3_HUMAN	Increases Expression	[11]
DNA mismatch repair protein Msh3 (MSH3)	OTD3YPVL	MSH3_HUMAN	Decreases Expression	[11]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[13]
Dual specificity protein phosphatase 1 (DUSP1)	OTN6BR75	DUS1_HUMAN	Increases Expression	[11]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[14]
Pro-adrenomedullin (ADM)	OT7T0TA4	ADML_HUMAN	Increases Expression	[11]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[14]
Collagen alpha-3(IV) chain (COL4A3)	OT6SB8X5	CO4A3_HUMAN	Increases Expression	[11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Expression	[15]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[14]
Solute carrier family 2, facilitated glucose transporter member 14 (SLC2A14)	OTBFIOVY	GTR14_HUMAN	Increases Expression	[11]
Protein NDRG1 (NDRG1)	OTVO66BO	NDRG1_HUMAN	Increases Expression	[11]
TSC22 domain family protein 3 (TSC22D3)	OT03UM03	T22D3_HUMAN	Increases Expression	[11]
Angiopoietin-related protein 4 (ANGPTL4)	OTQL5SPX	ANGL4_HUMAN	Increases Expression	[11]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[16]
Lysine-specific demethylase 3A (KDM3A)	OTZYJ8VN	KDM3A_HUMAN	Increases Expression	[11]
Hypoxia-inducible lipid droplet-associated protein (HILPDA)	OTEID3ZM	HLPDA_HUMAN	Increases Expression	[11]
Insulin-induced gene 2 protein (INSIG2)	OTX4VY51	INSI2_HUMAN	Increases Expression	[11]

Indication(s) of Romidepsin

Disease Entry	ICD 11	Status	REF
Cutaneous T-cell lymphoma	2B01	Approved	[3]
Gastrin-producing neuroendocrine tumor	N.A.	Approved	[4]
Glucagonoma	N.A.	Approved	[4]
Insulinoma	2C10.1	Approved	[4]
Lung carcinoid tumor	N.A.	Approved	[4]
Melanoma	2C30	Approved	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[4]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[4]
Urethral cancer	2C93	Approved	[4]
Peripheral T-cell lymphoma	2A90.C	Phase 3	[5]
Renal cell carcinoma	2C90	Phase 3	[3]

Romidepsin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[19]

Romidepsin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[20]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[20]

Romidepsin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[21]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[22]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[23]

Romidepsin Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[24]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Expression	[25]
E3 SUMO-protein ligase CBX4 (CBX4)	OT4XVRRF	CBX4_HUMAN	Increases Expression	[26]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[27]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[28]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[29]
Serine/threonine-protein kinase 17B (STK17B)	OT4NYNO8	ST17B_HUMAN	Increases Expression	[26]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[30]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Expression	[30]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[30]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[30]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[31]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Increases Expression	[26]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[30]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[18]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[26]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[31]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[30]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[31]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[18]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[18]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[32]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Phosphorylation	[18]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[26]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[30]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[31]
Friend leukemia integration 1 transcription factor (FLI1)	OT0EV3LX	FLI1_HUMAN	Decreases Expression	[34]
RNA-binding protein EWS (EWSR1)	OT7SRHV3	EWS_HUMAN	Decreases Expression	[34]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[18]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[32]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[26]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1)	OT6VY3A3	SPTN1_HUMAN	Increases Expression	[26]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Expression	[35]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[32]
Histone H3.1t (H3-4)	OTY6ITYF	H31T_HUMAN	Increases Acetylation	[35]
Sodium/iodide cotransporter (SLC5A5)	OTU7E9G7	SC5A5_HUMAN	Increases Expression	[36]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3)	OT53LJGW	M3K3_HUMAN	Increases Expression	[26]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Affects Metabolism	[37]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[38]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[31]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Lung adenocarcinoma	DC0PRXQ	EKVX	Investigative	[1]

References

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