Details of the Drug Combination

General Information of Drug Combination (ID: DCLGNS9)

• Drug Combination Name: Letrozole + Isoniazid
• Indication: Clear cell renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Letrozole (DMH07Y3): Small molecular drug
  Isoniazid (DM5JVS3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: 786-0
  Zero Interaction Potency (ZIP) Score: 0.42
  Bliss Independence Score: 2.8
  Loewe Additivity Score: 2.03
  LHighest Single Agent (HSA) Score: 2.03

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Letrozole

Disease Entry	ICD 11	Status	REF
Estrogen-receptor positive breast cancer	N.A.	Approved	[2]
Hormonally-responsive breast cancer	2C60-2C65	Approved	[3]

Letrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[6]

Letrozole Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[8]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[9]

Letrozole Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[10]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[11]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Oxidation	[11]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[12]
Dickkopf-related protein 1 (DKK1)	OTRDLUSP	DKK1_HUMAN	Increases Expression	[13]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[14]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[14]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[15]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[13]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[16]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[17]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[18]
Leukemia inhibitory factor receptor (LIFR)	OT36W9O5	LIFR_HUMAN	Increases Expression	[13]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[15]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[17]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Activity	[19]
Fibroblast growth factor 22 (FGF22)	OTVIX6J0	FGF22_HUMAN	Increases Expression	[13]

Indication(s) of Isoniazid

Disease Entry	ICD 11	Status	REF
Latent tuberculosis infection	N.A.	Approved	[4]
Pulmonary tuberculosis	1B10.Z	Approved	[4]
Tuberculosis	1B10-1B1Z	Approved	[5]

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	[21]

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	[22]
Catalase-peroxidase (katG)	DEAGY5M	KATG_SYNE7	Metabolism	[23]
Arylamine N-acetyltransferase (NAT)	DEXCQTM	A0A3P8LE58_TSUPA	Metabolism	[24]

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	[25]
N-alpha-acetyltransferase 20 (NAA20)	OTJB0VA6	NAA20_HUMAN	Increases ADR	[12]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[26]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[27]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[27]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[27]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Expression	[20]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[20]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Secretion	[20]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Secretion	[20]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[20]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[20]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[20]
Interleukin-12 subunit alpha (IL12A)	OTDQT8GI	IL12A_HUMAN	Increases Secretion	[20]
Interleukin-12 subunit beta (IL12B)	OT0JF8A3	IL12B_HUMAN	Increases Secretion	[20]
Interleukin-17A (IL17A)	OTY72FT2	IL17_HUMAN	Increases Secretion	[20]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[20]
Gamma-butyrobetaine dioxygenase (BBOX1)	OTKEX4RK	BODG_HUMAN	Increases Expression	[28]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Decreases Expression	[28]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)	OTTO6ZP4	AT1B1_HUMAN	Increases Expression	[28]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Increases Expression	[28]
Osteopontin (SPP1)	OTJGC23Y	OSTP_HUMAN	Decreases Expression	[28]
Mucin-1 (MUC1)	OTHQI7IY	MUC1_HUMAN	Increases Expression	[28]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[28]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Decreases Expression	[28]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Decreases Expression	[28]
Claudin-2 (CLDN2)	OTRF3D6Y	CLD2_HUMAN	Increases Expression	[28]
Large neutral amino acids transporter small subunit 1 (SLC7A5)	OT2WPVXD	LAT1_HUMAN	Decreases Expression	[28]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[28]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Increases Expression	[29]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Affects Expression	[30]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[31]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[31]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[32]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[31]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Activity	[33]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[33]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Decreases Activity	[33]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1)	OTQY6ZSF	HEM1_HUMAN	Increases Expression	[34]
Ferrochelatase, mitochondrial (FECH)	OTDWEI6C	HEMH_HUMAN	Decreases Expression	[34]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[25]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[25]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[31]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[35]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[33]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[33]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[25]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[31]
Nuclear respiratory factor 1 (NRF1)	OTOXWNV8	NRF1_HUMAN	Decreases Expression	[36]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1)	OT15YWU7	NR3L1_HUMAN	Increases Expression	[37]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[31]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[36]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[30]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Decreases Expression	[36]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Decreases Acetylation	[38]
Eosinophil peroxidase (EPX)	OTFNDFOK	PERE_HUMAN	Increases Oxidation	[39]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases Oxidation	[40]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[41]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Response To Substance	[42]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCOH5JU	HT29	Investigative	[1]
Astrocytoma	DCKNISM	U251	Investigative	[1]
Glioma	DC767YJ	SF-295	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DC1H20R	IGROV1	Investigative	[1]

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