Details of the Drug Combination

General Information of Drug Combination (ID: DC2E8HT)

• Drug Combination Name: Romidepsin + Mitotane
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  Romidepsin (DMT5GNL): Small molecular drug
  Mitotane (DMU1GX0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 6.587
  Bliss Independence Score: 6.832
  Loewe Additivity Score: 0.298
  LHighest Single Agent (HSA) Score: 3.639

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Romidepsin

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

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	[8]

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	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

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	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[12]

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	[13]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Expression	[14]
E3 SUMO-protein ligase CBX4 (CBX4)	OT4XVRRF	CBX4_HUMAN	Increases Expression	[15]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[16]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[17]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[18]
Serine/threonine-protein kinase 17B (STK17B)	OT4NYNO8	ST17B_HUMAN	Increases Expression	[15]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[19]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Expression	[19]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[19]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[19]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[20]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Increases Expression	[15]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[19]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[7]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[15]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[20]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[19]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[20]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[7]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[21]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Phosphorylation	[7]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[22]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[19]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[20]
Friend leukemia integration 1 transcription factor (FLI1)	OT0EV3LX	FLI1_HUMAN	Decreases Expression	[23]
RNA-binding protein EWS (EWSR1)	OT7SRHV3	EWS_HUMAN	Decreases Expression	[23]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[7]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[21]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[15]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1)	OT6VY3A3	SPTN1_HUMAN	Increases Expression	[15]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Expression	[24]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[21]
Histone H3.1t (H3-4)	OTY6ITYF	H31T_HUMAN	Increases Acetylation	[24]
Sodium/iodide cotransporter (SLC5A5)	OTU7E9G7	SC5A5_HUMAN	Increases Expression	[25]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3)	OT53LJGW	M3K3_HUMAN	Increases Expression	[15]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Affects Metabolism	[26]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[27]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[20]

Indication(s) of Mitotane

Disease Entry	ICD 11	Status	REF
Adrenocortical carcinoma	2D11.Z	Approved	[5]

Mitotane Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Binder	[28]

Mitotane Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 11B1, mitochondrial (CYP11B1)	OTKKL894	C11B1_HUMAN	Increases Expression	[29]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)	OT02MSKN	3BHS2_HUMAN	Decreases Expression	[29]
Cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A1)	OT2NV3AN	CP11A_HUMAN	Decreases Expression	[30]
Steroid 21-hydroxylase (CYP21A2)	OTN0UDVP	CP21A_HUMAN	Decreases Expression	[30]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Decreases Expression	[30]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[31]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[32]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[33]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Expression	[33]
cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A)	OT589JA2	KAP0_HUMAN	Decreases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[33]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[33]
Cytochrome c oxidase subunit 2 (COX2)	OTTMVBJJ	COX2_HUMAN	Decreases Expression	[34]
Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (COX4I1)	OTU0FC24	COX41_HUMAN	Decreases Expression	[34]
Cytochrome P450 11B2, mitochondrial (CYP11B2)	OTIOLWYN	C11B2_HUMAN	Decreases Expression	[34]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Decreases Expression	[35]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[35]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Activity	[36]
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Increases Expression	[37]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Affects Binding	[38]
Glia-derived nexin (SERPINE2)	OTYF5340	GDN_HUMAN	Increases Expression	[39]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[35]
Corticosteroid-binding globulin (SERPINA6)	OTOIBEW7	CBG_HUMAN	Increases Expression	[37]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Affects Binding	[38]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)	OTNAZVKB	3BHS1_HUMAN	Decreases Expression	[39]
Cyclic AMP-responsive element-binding protein 1 (CREB1)	OT1MDLA1	CREB1_HUMAN	Increases Activity	[40]
ETS domain-containing protein Elk-1 (ELK1)	OTH9MXD6	ELK1_HUMAN	Increases Activity	[40]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[35]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Increases Expression	[41]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Decreases Expression	[35]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Decreases Expression	[35]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Increases Activity	[40]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[35]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[42]
Mitochondrial 10-formyltetrahydrofolate dehydrogenase (ALDH1L2)	OTCH86VF	AL1L2_HUMAN	Increases Expression	[39]
Estrogen receptor beta (ESR2)	OTXNR2WQ	ESR2_HUMAN	Increases Activity	[36]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Decreases Expression	[35]
CREB-binding protein (CREBBP)	OTPA4QGM	CBP_HUMAN	Increases Activity	[43]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[39]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Increases Expression	[39]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Increases Response To Substance	[44]

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