Details of the Drug Combination

General Information of Drug Combination (ID: DC8OJ6W)

• Drug Combination Name: Dexrazoxane + Romidepsin
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  Dexrazoxane (DMD7X1O): Small molecular drug
  Romidepsin (DMT5GNL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: LOX IMVI
  Zero Interaction Potency (ZIP) Score: 0.43
  Bliss Independence Score: 1.05
  Loewe Additivity Score: 1.41
  LHighest Single Agent (HSA) Score: 3.37

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dexrazoxane

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Chemoprotection	N.A.	Approved	[3]
Inflammatory breast cancer	2C62	Approved	[4]
Respiratory tract disease	CB7Z	Investigative	[5]

Dexrazoxane Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II beta (TOP2B)	TT4NVEM	TOP2B_HUMAN	Inhibitor	[9]
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[10]

Dexrazoxane Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Dihydropyrimidinase-related protein 1 (DRP1)	DE0EUXB	DPYL1_HUMAN	Metabolism	[11]

Dexrazoxane Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Activity	[12]

Indication(s) of Romidepsin

Disease Entry	ICD 11	Status	REF
Cutaneous T-cell lymphoma	2B01	Approved	[6]
Gastrin-producing neuroendocrine tumor	N.A.	Approved	[7]
Glucagonoma	N.A.	Approved	[7]
Insulinoma	2C10.1	Approved	[7]
Lung carcinoid tumor	N.A.	Approved	[7]
Melanoma	2C30	Approved	[7]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[7]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[7]
Urethral cancer	2C93	Approved	[7]
Peripheral T-cell lymphoma	2A90.C	Phase 3	[8]
Renal cell carcinoma	2C90	Phase 3	[6]

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	[15]

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	[16]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[16]

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	[17]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[18]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[19]

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	[20]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Expression	[21]
E3 SUMO-protein ligase CBX4 (CBX4)	OT4XVRRF	CBX4_HUMAN	Increases Expression	[22]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[23]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[24]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[25]
Serine/threonine-protein kinase 17B (STK17B)	OT4NYNO8	ST17B_HUMAN	Increases Expression	[22]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[26]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Expression	[26]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[26]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[26]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[27]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Increases Expression	[22]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[26]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[14]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[22]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[27]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[26]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[27]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[14]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[14]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[28]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Phosphorylation	[14]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[22]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[29]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[27]
Friend leukemia integration 1 transcription factor (FLI1)	OT0EV3LX	FLI1_HUMAN	Decreases Expression	[30]
RNA-binding protein EWS (EWSR1)	OT7SRHV3	EWS_HUMAN	Decreases Expression	[30]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[14]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[28]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[22]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1)	OT6VY3A3	SPTN1_HUMAN	Increases Expression	[22]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Expression	[31]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[28]
Histone H3.1t (H3-4)	OTY6ITYF	H31T_HUMAN	Increases Acetylation	[31]
Sodium/iodide cotransporter (SLC5A5)	OTU7E9G7	SC5A5_HUMAN	Increases Expression	[32]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3)	OT53LJGW	M3K3_HUMAN	Increases Expression	[22]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Affects Metabolism	[33]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[34]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[27]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCZRTXP	SW-620	Investigative	[35]
Invasive ductal carcinoma	DCOIAZ6	BT-549	Investigative	[36]
Lung adenocarcinoma	DCYGFAR	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DC3I8JM	EKVX	Investigative	[1]
Melanoma	DC8510S	MALME-3M	Investigative	[1]

References

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