Details of the Drug Combination

General Information of Drug Combination (ID: DCAMSG7)

• Drug Combination Name: Romidepsin + Isoniazid
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Romidepsin (DMT5GNL): Small molecular drug
  Isoniazid (DM5JVS3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR-8
  Zero Interaction Potency (ZIP) Score: 5.08
  Bliss Independence Score: 2.88
  Loewe Additivity Score: 2.46
  LHighest Single Agent (HSA) Score: 2.12

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	[9]

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	[10]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[10]

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	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[13]

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	[14]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Expression	[15]
E3 SUMO-protein ligase CBX4 (CBX4)	OT4XVRRF	CBX4_HUMAN	Increases Expression	[16]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[17]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[18]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[19]
Serine/threonine-protein kinase 17B (STK17B)	OT4NYNO8	ST17B_HUMAN	Increases Expression	[16]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[20]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Expression	[20]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[20]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[20]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[21]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Increases Expression	[16]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[20]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[8]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[16]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[21]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[20]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[8]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[8]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[22]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Phosphorylation	[8]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[20]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[21]
Friend leukemia integration 1 transcription factor (FLI1)	OT0EV3LX	FLI1_HUMAN	Decreases Expression	[24]
RNA-binding protein EWS (EWSR1)	OT7SRHV3	EWS_HUMAN	Decreases Expression	[24]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[22]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[16]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1)	OT6VY3A3	SPTN1_HUMAN	Increases Expression	[16]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Expression	[25]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[22]
Histone H3.1t (H3-4)	OTY6ITYF	H31T_HUMAN	Increases Acetylation	[25]
Sodium/iodide cotransporter (SLC5A5)	OTU7E9G7	SC5A5_HUMAN	Increases Expression	[26]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3)	OT53LJGW	M3K3_HUMAN	Increases Expression	[16]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Affects Metabolism	[27]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[28]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[21]

Indication(s) of Isoniazid

Disease Entry	ICD 11	Status	REF
Latent tuberculosis infection	N.A.	Approved	[5]
Pulmonary tuberculosis	1B10.Z	Approved	[5]
Tuberculosis	1B10-1B1Z	Approved	[6]

Isoniazid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Fatty acid synthetase I (Bact inhA)	TTVTX4N	INHA_MYCTU	Inhibitor	[30]

Isoniazid Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[31]
Catalase-peroxidase (katG)	DEAGY5M	KATG_SYNE7	Metabolism	[32]
Arylamine N-acetyltransferase (NAT)	DEXCQTM	A0A3P8LE58_TSUPA	Metabolism	[33]

Isoniazid Interacts with 59 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Expression	[34]
N-alpha-acetyltransferase 20 (NAA20)	OTJB0VA6	NAA20_HUMAN	Increases ADR	[35]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[36]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[37]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[37]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[37]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Expression	[29]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[29]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Secretion	[29]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Secretion	[29]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[29]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[29]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[29]
Interleukin-12 subunit alpha (IL12A)	OTDQT8GI	IL12A_HUMAN	Increases Secretion	[29]
Interleukin-12 subunit beta (IL12B)	OT0JF8A3	IL12B_HUMAN	Increases Secretion	[29]
Interleukin-17A (IL17A)	OTY72FT2	IL17_HUMAN	Increases Secretion	[29]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[29]
Gamma-butyrobetaine dioxygenase (BBOX1)	OTKEX4RK	BODG_HUMAN	Increases Expression	[38]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Decreases Expression	[38]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)	OTTO6ZP4	AT1B1_HUMAN	Increases Expression	[38]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Increases Expression	[38]
Osteopontin (SPP1)	OTJGC23Y	OSTP_HUMAN	Decreases Expression	[38]
Mucin-1 (MUC1)	OTHQI7IY	MUC1_HUMAN	Increases Expression	[38]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[38]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Decreases Expression	[38]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Decreases Expression	[38]
Claudin-2 (CLDN2)	OTRF3D6Y	CLD2_HUMAN	Increases Expression	[38]
Large neutral amino acids transporter small subunit 1 (SLC7A5)	OT2WPVXD	LAT1_HUMAN	Decreases Expression	[38]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[38]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Increases Expression	[39]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Affects Expression	[40]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[41]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[41]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[42]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[41]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Activity	[43]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[43]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Decreases Activity	[43]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1)	OTQY6ZSF	HEM1_HUMAN	Increases Expression	[44]
Ferrochelatase, mitochondrial (FECH)	OTDWEI6C	HEMH_HUMAN	Decreases Expression	[44]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[34]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[34]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[41]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[45]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[43]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[43]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[34]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[41]
Nuclear respiratory factor 1 (NRF1)	OTOXWNV8	NRF1_HUMAN	Decreases Expression	[46]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1)	OT15YWU7	NR3L1_HUMAN	Increases Expression	[47]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[41]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[46]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[40]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Decreases Expression	[46]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Decreases Acetylation	[48]
Eosinophil peroxidase (EPX)	OTFNDFOK	PERE_HUMAN	Increases Oxidation	[49]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases Oxidation	[50]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[51]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Response To Substance	[52]

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