Details of the Drug Combination

General Information of Drug Combination (ID: DC51VK7)

• Drug Combination Name: Liothyronine + Tranylcypromine
• Indication: Major Depression; Status: Phase 4 [1]
• Component Drugs:
  Liothyronine (DM6IR3P): Small molecular drug
  Tranylcypromine (DMGB5RE): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Liothyronine

Disease Entry	ICD 11	Status	REF
Congenital hypothyroidism	N.A.	Approved	[2]
Edema	MG29	Approved	[2]
Goiter	N.A.	Approved	[2]
Hypothyroidism	5A00	Approved	[3]
Thyroid cancer	2D10	Approved	[2]
Congestive heart failure	BD10	Phase 3	[4]

Liothyronine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Thyroid hormone receptor alpha (THRA)	TTTSEPU	THA_HUMAN	Antagonist	[8]

Liothyronine Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[12]
Organic anion transporting polypeptide 1C1 (SLCO1C1)	DTPYCQ4	SO1C1_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 4A1 (SLCO4A1)	DT8H2IC	SO4A1_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTY0QMU	SO4C1_HUMAN	Substrate	[14]

Liothyronine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[15]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[16]

Liothyronine Interacts with 126 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Sulfotransferase 1A1 (SULT1A1)	OT0K7JIE	ST1A1_HUMAN	Increases Sulfation	[16]
Monocarboxylate transporter 4 (SLC16A3)	OTDIXEXY	MOT4_HUMAN	Increases Expression	[17]
All-trans-retinol dehydrogenase ADH1B (ADH1B)	OTV3TB81	ADH1B_HUMAN	Decreases Expression	[17]
Alpha-enolase (ENO1)	OTB1KWJS	ENOA_HUMAN	Increases Expression	[17]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases Expression	[17]
Collagen alpha-3(VI) chain (COL6A3)	OTAS6R6I	CO6A3_HUMAN	Increases Expression	[17]
Ras-related protein Rab-3B (RAB3B)	OTZA4SXL	RAB3B_HUMAN	Increases Expression	[17]
Fibroblast growth factor 7 (FGF7)	OTGK6ANL	FGF7_HUMAN	Decreases Expression	[17]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Increases Expression	[17]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Increases Expression	[17]
ATP-dependent 6-phosphofructokinase, platelet type (PFKP)	OTFP7AA8	PFKAP_HUMAN	Increases Expression	[17]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Increases Expression	[17]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[17]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Decreases Expression	[18]
Monocarboxylate transporter 7 (SLC16A6)	OT7BIIZX	MOT7_HUMAN	Increases Expression	[19]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[19]
Stromelysin-3 (MMP11)	OTRTXDBM	MMP11_HUMAN	Increases Expression	[19]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Increases Expression	[19]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Increases Expression	[19]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Increases Expression	[19]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[19]
Transcriptional and immune response regulator (TCIM)	OTARUXQF	TCIM_HUMAN	Increases Expression	[19]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[20]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[20]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Increases Expression	[20]
Uncharacterized protein C20orf204 (C20ORF204)	OT0GVQPP	CT204_HUMAN	Decreases Expression	[6]
Meiosis-specific coiled-coil domain-containing protein MEIOC (MEIOC)	OTME1FFG	MEIOC_HUMAN	Decreases Expression	[6]
LYR motif-containing protein 9 (LYRM9)	OT1MILTK	LYRM9_HUMAN	Decreases Expression	[6]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Increases Phosphorylation	[21]
Apolipoprotein L1 (APOL1)	OT8QBVTY	APOL1_HUMAN	Decreases Expression	[6]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[22]
Serine palmitoyltransferase 2 (SPTLC2)	OTBTMH1Z	SPTC2_HUMAN	Increases Expression	[6]
Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12)	OTZKOTDB	ADA12_HUMAN	Increases Expression	[6]
Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2)	OTR7WJES	DC1L2_HUMAN	Increases Expression	[6]
Trans-Golgi network integral membrane protein 2 (TGOLN2)	OTM647IV	TGON2_HUMAN	Decreases Expression	[6]
Lysine-specific demethylase hairless (HR)	OTHEZWPW	HAIR_HUMAN	Increases Expression	[23]
Prostate stem cell antigen (PSCA)	OTQ574EY	PSCA_HUMAN	Increases Expression	[24]
Plexin-C1 (PLXNC1)	OTJ5XKYY	PLXC1_HUMAN	Increases Expression	[6]
TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L)	OTCP6ZYD	TAF5L_HUMAN	Increases Expression	[6]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[25]
Echinoderm microtubule-associated protein-like 2 (EML2)	OTRX2NTA	EMAL2_HUMAN	Increases Expression	[6]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Increases Expression	[26]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[22]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[22]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[27]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[28]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[22]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Decreases Expression	[29]
Thyroxine-binding globulin (SERPINA7)	OTUYVTSU	THBG_HUMAN	Affects Binding	[7]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Expression	[30]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[6]
Histone H2A type 1 (H2AC11)	OTN9P0BO	H2A1_HUMAN	Decreases Expression	[6]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[22]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[31]
Thyroid hormone receptor beta (THRB)	OTBBIRHZ	THB_HUMAN	Increases Expression	[32]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Affects Binding	[21]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Increases Expression	[24]
Replication protein A 32 kDa subunit (RPA2)	OTZ54WAF	RFA2_HUMAN	Increases Phosphorylation	[21]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[21]
Histone H1.5 (H1-5)	OTAN7RD9	H15_HUMAN	Increases Expression	[6]
Neuroendocrine convertase 2 (PCSK2)	OT9Y2Z9B	NEC2_HUMAN	Decreases Expression	[33]
Integrin beta-5 (ITGB5)	OT21MF51	ITB5_HUMAN	Decreases Expression	[6]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Expression	[31]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[25]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[24]
Interleukin-32 (IL32)	OT3FHZ81	IL32_HUMAN	Increases Expression	[24]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Increases Expression	[31]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Increases Expression	[31]
Neuroendocrine convertase 1 (PCSK1)	OTPBRJ54	NEC1_HUMAN	Decreases Expression	[34]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[31]
Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3)	OTODTW0I	HNRH3_HUMAN	Increases Expression	[6]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[22]
Beta-adducin (ADD2)	OTRCPCD2	ADDB_HUMAN	Increases Expression	[6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[24]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[31]
Solute carrier family 15 member 1 (SLC15A1)	OT1P16B5	S15A1_HUMAN	Decreases Expression	[35]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Decreases Expression	[31]
Inactive serine/threonine-protein kinase 19 (STK19)	OTYM6437	STK19_HUMAN	Increases Expression	[6]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Increases Expression	[36]
Peroxisomal targeting signal 1 receptor (PEX5)	OTK4LMG7	PEX5_HUMAN	Increases Expression	[6]
Protein HIRA (HIRA)	OTON40EJ	HIRA_HUMAN	Increases Expression	[6]
Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2)	OTC3RUN9	HMCS2_HUMAN	Increases Expression	[6]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Increases Expression	[6]
A-kinase anchor protein 12 (AKAP12)	OTCVRDDX	AKA12_HUMAN	Increases Expression	[6]
Dual specificity protein phosphatase 2 (DUSP2)	OTH54FMR	DUS2_HUMAN	Decreases Expression	[24]
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9)	OTNOM26L	TNR9_HUMAN	Increases Expression	[24]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[31]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Increases Expression	[31]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[22]
Pregnancy-specific beta-1-glycoprotein 7 (PSG7)	OT1IXGBX	PSG7_HUMAN	Increases Expression	[24]
TNF receptor-associated factor 1 (TRAF1)	OTTLM5RU	TRAF1_HUMAN	Increases Expression	[24]
Disintegrin and metalloproteinase domain-containing protein 15 (ADAM15)	OTZ7VLTP	ADA15_HUMAN	Decreases Expression	[6]
Krueppel-like factor 9 (KLF9)	OTBFEJRQ	KLF9_HUMAN	Decreases Expression	[6]
Glutamate receptor ionotropic, kainate 4 (GRIK4)	OTL5EIPA	GRIK4_HUMAN	Increases Expression	[6]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Increases Expression	[36]
Tigger transposable element-derived protein 6 (TIGD6)	OT8S6ZQW	TIGD6_HUMAN	Increases Expression	[6]
Transmembrane protein 44 (TMEM44)	OTRUF467	TMM44_HUMAN	Increases Expression	[6]
Akirin-2 (AKIRIN2)	OTQ6WSKW	AKIR2_HUMAN	Increases Expression	[6]
Protein FAM171B (FAM171B)	OT4DJHCM	F171B_HUMAN	Decreases Expression	[6]
Protein FAM83H (FAM83H)	OTN0SF11	FA83H_HUMAN	Increases Expression	[6]
Butyrophilin subfamily 2 member A1 (BTN2A1)	OTUYPMZJ	BT2A1_HUMAN	Decreases Expression	[6]
Mesoderm induction early response protein 3 (MIER3)	OTL5BGOB	MIER3_HUMAN	Decreases Expression	[6]
Tripartite motif-containing protein 46 (TRIM46)	OTFE7WZW	TRI46_HUMAN	Increases Expression	[6]
Retrotransposon-derived protein PEG10 (PEG10)	OTWD2278	PEG10_HUMAN	Increases Expression	[6]
Rho guanine nucleotide exchange factor 25 (ARHGEF25)	OT7162TD	ARHGP_HUMAN	Decreases Expression	[6]
Condensin-2 complex subunit G2 (NCAPG2)	OTZYENKO	CNDG2_HUMAN	Decreases Expression	[6]
Coiled-coil domain-containing protein 71 (CCDC71)	OT4TJ7K8	CCD71_HUMAN	Decreases Expression	[6]
Iron-sulfur cluster co-chaperone protein HscB (HSCB)	OTP8YV25	HSC20_HUMAN	Decreases Expression	[6]
Abnormal spindle-like microcephaly-associated protein (ASPM)	OTKXQMNA	ASPM_HUMAN	Decreases Expression	[6]
EF-hand calcium-binding domain-containing protein 4A (CRACR2B)	OT8L843R	EFC4A_HUMAN	Decreases Expression	[6]
EF-hand calcium-binding domain-containing protein 3 (EFCAB3)	OT7CUMLL	EFCB3_HUMAN	Decreases Expression	[6]
Inactive phospholipase D5 (PLD5)	OTEVPYNY	PLD5_HUMAN	Increases Expression	[6]
Acyl-CoA-binding domain-containing protein 4 (ACBD4)	OTVR7MLK	ACBD4_HUMAN	Decreases Expression	[6]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Expression	[31]
Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10)	OTYKLW1K	FKB10_HUMAN	Decreases Expression	[6]
Rho-related GTP-binding protein RhoV (RHOV)	OTW4N3QN	RHOV_HUMAN	Increases Expression	[6]
Msx2-interacting protein (SPEN)	OT37A2MD	MINT_HUMAN	Increases Expression	[6]
PTB domain-containing engulfment adapter protein 1 (GULP1)	OT1WMVDH	GULP1_HUMAN	Decreases Expression	[6]
LIM/homeobox protein Lhx3 (LHX3)	OTQ5BAJ9	LHX3_HUMAN	Decreases Expression	[6]
Protein mono-ADP-ribosyltransferase PARP4 (PARP4)	OTXBK59G	PARP4_HUMAN	Decreases Expression	[6]
Ras-related protein Rab-23 (RAB23)	OTBAKFBR	RAB23_HUMAN	Decreases Expression	[6]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[22]
Sulfotransferase 4A1 (SULT4A1)	OT7AL3KJ	ST4A1_HUMAN	Increases Metabolism	[37]
Thyrotropin subunit beta (TSHB)	OTFDI39D	TSHB_HUMAN	Increases Secretion	[38]
Type I iodothyronine deiodinase (DIO1)	OTFYLYJ0	IOD1_HUMAN	Increases Chemical Synthesis	[39]
Monocarboxylate transporter 8 (SLC16A2)	OTLRA7C0	MOT8_HUMAN	Increases Uptake	[40]

Indication(s) of Tranylcypromine

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[3]
Prostate cancer	2C82.0	Patented	[5]

Tranylcypromine Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Inhibitor	[5]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[41]
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[42]

Tranylcypromine Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Decreases Activity	[43]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Decreases Activity	[44]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[45]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[46]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Activity	[47]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Decreases Activity	[48]

References

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• [2] Liothyronine FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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