Details of the Drug Combination

General Information of Drug Combination (ID: DCE3BTD)

• Drug Combination Name: Isoniazid + Methadone
• Indication: Opioid Dependence; Status: Phase 1 [1]
• Component Drugs:
  Isoniazid (DM5JVS3): Small molecular drug
  Methadone (DMTW6IU): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Isoniazid

Disease Entry	ICD 11	Status	REF
Latent tuberculosis infection	N.A.	Approved	[2]
Pulmonary tuberculosis	1B10.Z	Approved	[2]
Tuberculosis	1B10-1B1Z	Approved	[3]

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	[7]

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	[8]
Catalase-peroxidase (katG)	DEAGY5M	KATG_SYNE7	Metabolism	[9]
Arylamine N-acetyltransferase (NAT)	DEXCQTM	A0A3P8LE58_TSUPA	Metabolism	[10]

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	[11]
N-alpha-acetyltransferase 20 (NAA20)	OTJB0VA6	NAA20_HUMAN	Increases ADR	[12]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[13]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[14]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[14]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[14]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Expression	[6]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[6]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Secretion	[6]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Secretion	[6]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[6]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[6]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[6]
Interleukin-12 subunit alpha (IL12A)	OTDQT8GI	IL12A_HUMAN	Increases Secretion	[6]
Interleukin-12 subunit beta (IL12B)	OT0JF8A3	IL12B_HUMAN	Increases Secretion	[6]
Interleukin-17A (IL17A)	OTY72FT2	IL17_HUMAN	Increases Secretion	[6]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[6]
Gamma-butyrobetaine dioxygenase (BBOX1)	OTKEX4RK	BODG_HUMAN	Increases Expression	[15]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Decreases Expression	[15]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)	OTTO6ZP4	AT1B1_HUMAN	Increases Expression	[15]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Increases Expression	[15]
Osteopontin (SPP1)	OTJGC23Y	OSTP_HUMAN	Decreases Expression	[15]
Mucin-1 (MUC1)	OTHQI7IY	MUC1_HUMAN	Increases Expression	[15]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[15]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Decreases Expression	[15]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Decreases Expression	[15]
Claudin-2 (CLDN2)	OTRF3D6Y	CLD2_HUMAN	Increases Expression	[15]
Large neutral amino acids transporter small subunit 1 (SLC7A5)	OT2WPVXD	LAT1_HUMAN	Decreases Expression	[15]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[15]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Increases Expression	[16]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Affects Expression	[17]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[18]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[19]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[18]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Activity	[20]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[20]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Decreases Activity	[20]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1)	OTQY6ZSF	HEM1_HUMAN	Increases Expression	[21]
Ferrochelatase, mitochondrial (FECH)	OTDWEI6C	HEMH_HUMAN	Decreases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[11]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[11]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[18]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[22]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[20]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[20]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[11]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[18]
Nuclear respiratory factor 1 (NRF1)	OTOXWNV8	NRF1_HUMAN	Decreases Expression	[23]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1)	OT15YWU7	NR3L1_HUMAN	Increases Expression	[24]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[18]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[23]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[17]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Decreases Expression	[23]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Decreases Acetylation	[25]
Eosinophil peroxidase (EPX)	OTFNDFOK	PERE_HUMAN	Increases Oxidation	[26]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases Oxidation	[27]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[28]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Response To Substance	[29]

Indication(s) of Methadone

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[4]
Dry cough	MD12	Approved	[5]
Pain	MG30-MG3Z	Approved	[4]

Methadone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Agonist	[30]

Methadone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[31]

Methadone Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[32]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[33]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[34]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[32]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[32]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[35]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[32]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[32]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[32]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[32]

Methadone Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[36]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[37]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Affects Binding	[38]
Phospholipase D2 (PLD2)	OT86I3WH	PLD2_HUMAN	Increases Activity	[39]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[40]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Response To Substance	[41]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Expression	[39]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Binding	[42]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[43]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[39]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[39]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases Expression	[44]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[39]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[45]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Localization	[45]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[46]

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