Details of the Drug Combination

General Information of Drug Combination (ID: DCIB9X3)

• Drug Combination Name: Sertraline + Liothyronine
• Indication: Major Depression; Status: Phase 1 [1]
• Component Drugs:
  Sertraline (DM0FB1J): Small molecular drug
  Liothyronine (DM6IR3P): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sertraline

Disease Entry	ICD 11	Status	REF
Coronary heart disease	BA80.Z	Approved	[2]
Depression	6A70-6A7Z	Approved	[3]
Epilepsy	8A60-8A68	Approved	[2]
Obsessive compulsive disorder	6B20	Approved	[2]
Panic disorder	6B01	Approved	[2]
Post-traumatic stress disorder	6B40	Approved	[2]

Sertraline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[11]

Sertraline Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Sertraline Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[14]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[15]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[17]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[18]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[18]

Sertraline Interacts with 88 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Activity	[19]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[20]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Methylation	[21]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Activity	[22]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH)	OTUG4BWA	PAHX_HUMAN	Increases Expression	[7]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[7]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[7]
Serine protease hepsin (HPN)	OT7QNA61	HEPS_HUMAN	Increases Expression	[7]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Increases Expression	[7]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[7]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[7]
Lanosterol synthase (LSS)	OT9W2SFH	LSS_HUMAN	Increases Expression	[7]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[7]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[7]
Acid ceramidase (ASAH1)	OT1DNGXL	ASAH1_HUMAN	Increases Expression	[7]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[7]
Lysophospholipase D GDPD3 (GDPD3)	OTOHM9QM	GDPD3_HUMAN	Increases Expression	[7]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[7]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[7]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[23]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Expression	[23]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[24]
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13)	OTS93BTX	M3K13_HUMAN	Increases Expression	[8]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[8]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[8]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A)	OTYG179K	PR15A_HUMAN	Increases Expression	[8]
Dual specificity protein phosphatase 14 (DUSP14)	OTGODFCR	DUS14_HUMAN	Increases Expression	[8]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)	OTBMJUOC	M4K4_HUMAN	Decreases Expression	[8]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Expression	[8]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[8]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[25]
Alpha-crystallin A chain (CRYAA)	OTSN7JUR	CRYAA_HUMAN	Increases Expression	[8]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[26]
Platelet basic protein (PPBP)	OT1FHGQS	CXCL7_HUMAN	Decreases Expression	[27]
Platelet factor 4 (PF4)	OTEMJU68	PLF4_HUMAN	Decreases Expression	[9]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[8]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[8]
Transcription factor AP-2-alpha (TFAP2A)	OTMYT3NK	AP2A_HUMAN	Increases Expression	[28]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Decreases Expression	[8]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Increases Expression	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[25]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Decreases Expression	[8]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2)	OTNIZPEA	ATF2_HUMAN	Increases Expression	[8]
P-selectin (SELP)	OTWR90PK	LYAM3_HUMAN	Decreases Expression	[27]
Platelet endothelial cell adhesion molecule (PECAM1)	OTXOM4D9	PECA1_HUMAN	Decreases Expression	[9]
E-selectin (SELE)	OT33RZWY	LYAM2_HUMAN	Decreases Expression	[27]
Stathmin (STMN1)	OTDJ4RV0	STMN1_HUMAN	Decreases Expression	[8]
Heat shock 70 kDa protein 6 (HSPA6)	OTH4S7WB	HSP76_HUMAN	Increases Expression	[8]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[8]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[8]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[8]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[10]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[8]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[25]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[25]
Dual specificity protein phosphatase 1 (DUSP1)	OTN6BR75	DUS1_HUMAN	Increases Expression	[8]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[8]
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8)	OTOZTA1F	M3K8_HUMAN	Increases Expression	[8]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[8]
Translocon-associated protein subunit beta (SSR2)	OTQJSL7M	SSRB_HUMAN	Increases Expression	[8]
Caspase-4 (CASP4)	OTVQTV1L	CASP4_HUMAN	Increases Cleavage	[8]
Ribosomal protein S6 kinase alpha-3 (RPS6KA3)	OTYJNNMD	KS6A3_HUMAN	Decreases Expression	[8]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[8]
Protein transport protein Sec61 subunit gamma (SEC61G)	OT7MJRXY	SC61G_HUMAN	Decreases Expression	[8]
E3 ubiquitin-protein ligase RBX1 (RBX1)	OTYA1UIO	RBX1_HUMAN	Decreases Expression	[8]
S-phase kinase-associated protein 1 (SKP1)	OT5BPAZ4	SKP1_HUMAN	Decreases Expression	[8]
Nuclear factor NF-kappa-B p100 subunit (NFKB2)	OTS231V7	NFKB2_HUMAN	Increases Expression	[8]
Transcription factor RelB (RELB)	OTU3QYEF	RELB_HUMAN	Increases Expression	[8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[25]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[29]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[10]
Dual specificity protein phosphatase 8 (DUSP8)	OTPLMPG9	DUS8_HUMAN	Increases Expression	[8]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[10]
Cullin-1 (CUL1)	OTXPE1UZ	CUL1_HUMAN	Decreases Expression	[8]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1)	OT9EROL6	HERP1_HUMAN	Increases Expression	[8]
Serine/threonine-protein kinase STK11 (STK11)	OT1YZSP3	STK11_HUMAN	Increases Phosphorylation	[10]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[8]
E3 ubiquitin-protein ligase synoviolin (SYVN1)	OTZ4ZJP5	SYVN1_HUMAN	Increases Expression	[8]
Dual specificity protein phosphatase 16 (DUSP16)	OTK7S078	DUS16_HUMAN	Increases Expression	[8]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Lipidation	[10]
DnaJ homolog subfamily C member 5 (DNAJC5)	OTCZDXAL	DNJC5_HUMAN	Increases Expression	[30]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Expression	[8]
Serine/threonine-protein kinase TAO2 (TAOK2)	OTNUMOZ1	TAOK2_HUMAN	Increases Expression	[8]
C-Jun-amino-terminal kinase-interacting protein 3 (MAPK8IP3)	OT0X8ACY	JIP3_HUMAN	Increases Expression	[8]
Dual specificity protein phosphatase 10 (DUSP10)	OTNG467B	DUS10_HUMAN	Increases Expression	[8]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Increases Response To Substance	[31]

Indication(s) of Liothyronine

Disease Entry	ICD 11	Status	REF
Congenital hypothyroidism	N.A.	Approved	[4]
Edema	MG29	Approved	[4]
Goiter	N.A.	Approved	[4]
Hypothyroidism	5A00	Approved	[5]
Thyroid cancer	2D10	Approved	[4]
Congestive heart failure	BD10	Phase 3	[6]

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	[34]

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	[35]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[36]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[37]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[38]
Organic anion transporting polypeptide 1C1 (SLCO1C1)	DTPYCQ4	SO1C1_HUMAN	Substrate	[39]
Organic anion transporting polypeptide 4A1 (SLCO4A1)	DT8H2IC	SO4A1_HUMAN	Substrate	[40]
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTY0QMU	SO4C1_HUMAN	Substrate	[40]

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	[41]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[42]

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	[42]
Monocarboxylate transporter 4 (SLC16A3)	OTDIXEXY	MOT4_HUMAN	Increases Expression	[43]
All-trans-retinol dehydrogenase ADH1B (ADH1B)	OTV3TB81	ADH1B_HUMAN	Decreases Expression	[43]
Alpha-enolase (ENO1)	OTB1KWJS	ENOA_HUMAN	Increases Expression	[43]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases Expression	[43]
Collagen alpha-3(VI) chain (COL6A3)	OTAS6R6I	CO6A3_HUMAN	Increases Expression	[43]
Ras-related protein Rab-3B (RAB3B)	OTZA4SXL	RAB3B_HUMAN	Increases Expression	[43]
Fibroblast growth factor 7 (FGF7)	OTGK6ANL	FGF7_HUMAN	Decreases Expression	[43]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Increases Expression	[43]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Increases Expression	[43]
ATP-dependent 6-phosphofructokinase, platelet type (PFKP)	OTFP7AA8	PFKAP_HUMAN	Increases Expression	[43]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Increases Expression	[43]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[43]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Decreases Expression	[44]
Monocarboxylate transporter 7 (SLC16A6)	OT7BIIZX	MOT7_HUMAN	Increases Expression	[45]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[45]
Stromelysin-3 (MMP11)	OTRTXDBM	MMP11_HUMAN	Increases Expression	[45]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Increases Expression	[45]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Increases Expression	[45]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Increases Expression	[45]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[45]
Transcriptional and immune response regulator (TCIM)	OTARUXQF	TCIM_HUMAN	Increases Expression	[45]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[46]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[46]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Increases Expression	[46]
Uncharacterized protein C20orf204 (C20ORF204)	OT0GVQPP	CT204_HUMAN	Decreases Expression	[32]
Meiosis-specific coiled-coil domain-containing protein MEIOC (MEIOC)	OTME1FFG	MEIOC_HUMAN	Decreases Expression	[32]
LYR motif-containing protein 9 (LYRM9)	OT1MILTK	LYRM9_HUMAN	Decreases Expression	[32]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Increases Phosphorylation	[47]
Apolipoprotein L1 (APOL1)	OT8QBVTY	APOL1_HUMAN	Decreases Expression	[32]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[48]
Serine palmitoyltransferase 2 (SPTLC2)	OTBTMH1Z	SPTC2_HUMAN	Increases Expression	[32]
Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12)	OTZKOTDB	ADA12_HUMAN	Increases Expression	[32]
Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2)	OTR7WJES	DC1L2_HUMAN	Increases Expression	[32]
Trans-Golgi network integral membrane protein 2 (TGOLN2)	OTM647IV	TGON2_HUMAN	Decreases Expression	[32]
Lysine-specific demethylase hairless (HR)	OTHEZWPW	HAIR_HUMAN	Increases Expression	[49]
Prostate stem cell antigen (PSCA)	OTQ574EY	PSCA_HUMAN	Increases Expression	[50]
Plexin-C1 (PLXNC1)	OTJ5XKYY	PLXC1_HUMAN	Increases Expression	[32]
TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L)	OTCP6ZYD	TAF5L_HUMAN	Increases Expression	[32]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[51]
Echinoderm microtubule-associated protein-like 2 (EML2)	OTRX2NTA	EMAL2_HUMAN	Increases Expression	[32]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Increases Expression	[52]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[48]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[48]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[53]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[54]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[48]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Decreases Expression	[55]
Thyroxine-binding globulin (SERPINA7)	OTUYVTSU	THBG_HUMAN	Affects Binding	[33]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Expression	[56]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[32]
Histone H2A type 1 (H2AC11)	OTN9P0BO	H2A1_HUMAN	Decreases Expression	[32]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[48]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[57]
Thyroid hormone receptor beta (THRB)	OTBBIRHZ	THB_HUMAN	Increases Expression	[58]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Affects Binding	[47]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Increases Expression	[50]
Replication protein A 32 kDa subunit (RPA2)	OTZ54WAF	RFA2_HUMAN	Increases Phosphorylation	[47]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[47]
Histone H1.5 (H1-5)	OTAN7RD9	H15_HUMAN	Increases Expression	[32]
Neuroendocrine convertase 2 (PCSK2)	OT9Y2Z9B	NEC2_HUMAN	Decreases Expression	[59]
Integrin beta-5 (ITGB5)	OT21MF51	ITB5_HUMAN	Decreases Expression	[32]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Expression	[57]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[51]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[50]
Interleukin-32 (IL32)	OT3FHZ81	IL32_HUMAN	Increases Expression	[50]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Increases Expression	[57]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Increases Expression	[57]
Neuroendocrine convertase 1 (PCSK1)	OTPBRJ54	NEC1_HUMAN	Decreases Expression	[60]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[57]
Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3)	OTODTW0I	HNRH3_HUMAN	Increases Expression	[32]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[48]
Beta-adducin (ADD2)	OTRCPCD2	ADDB_HUMAN	Increases Expression	[32]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[50]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[57]
Solute carrier family 15 member 1 (SLC15A1)	OT1P16B5	S15A1_HUMAN	Decreases Expression	[61]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Decreases Expression	[57]
Inactive serine/threonine-protein kinase 19 (STK19)	OTYM6437	STK19_HUMAN	Increases Expression	[32]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Increases Expression	[62]
Peroxisomal targeting signal 1 receptor (PEX5)	OTK4LMG7	PEX5_HUMAN	Increases Expression	[32]
Protein HIRA (HIRA)	OTON40EJ	HIRA_HUMAN	Increases Expression	[32]
Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2)	OTC3RUN9	HMCS2_HUMAN	Increases Expression	[32]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Increases Expression	[32]
A-kinase anchor protein 12 (AKAP12)	OTCVRDDX	AKA12_HUMAN	Increases Expression	[32]
Dual specificity protein phosphatase 2 (DUSP2)	OTH54FMR	DUS2_HUMAN	Decreases Expression	[50]
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9)	OTNOM26L	TNR9_HUMAN	Increases Expression	[50]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[57]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Increases Expression	[57]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[48]
Pregnancy-specific beta-1-glycoprotein 7 (PSG7)	OT1IXGBX	PSG7_HUMAN	Increases Expression	[50]
TNF receptor-associated factor 1 (TRAF1)	OTTLM5RU	TRAF1_HUMAN	Increases Expression	[50]
Disintegrin and metalloproteinase domain-containing protein 15 (ADAM15)	OTZ7VLTP	ADA15_HUMAN	Decreases Expression	[32]
Krueppel-like factor 9 (KLF9)	OTBFEJRQ	KLF9_HUMAN	Decreases Expression	[32]
Glutamate receptor ionotropic, kainate 4 (GRIK4)	OTL5EIPA	GRIK4_HUMAN	Increases Expression	[32]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Increases Expression	[62]
Tigger transposable element-derived protein 6 (TIGD6)	OT8S6ZQW	TIGD6_HUMAN	Increases Expression	[32]
Transmembrane protein 44 (TMEM44)	OTRUF467	TMM44_HUMAN	Increases Expression	[32]
Akirin-2 (AKIRIN2)	OTQ6WSKW	AKIR2_HUMAN	Increases Expression	[32]
Protein FAM171B (FAM171B)	OT4DJHCM	F171B_HUMAN	Decreases Expression	[32]
Protein FAM83H (FAM83H)	OTN0SF11	FA83H_HUMAN	Increases Expression	[32]
Butyrophilin subfamily 2 member A1 (BTN2A1)	OTUYPMZJ	BT2A1_HUMAN	Decreases Expression	[32]
Mesoderm induction early response protein 3 (MIER3)	OTL5BGOB	MIER3_HUMAN	Decreases Expression	[32]
Tripartite motif-containing protein 46 (TRIM46)	OTFE7WZW	TRI46_HUMAN	Increases Expression	[32]
Retrotransposon-derived protein PEG10 (PEG10)	OTWD2278	PEG10_HUMAN	Increases Expression	[32]
Rho guanine nucleotide exchange factor 25 (ARHGEF25)	OT7162TD	ARHGP_HUMAN	Decreases Expression	[32]
Condensin-2 complex subunit G2 (NCAPG2)	OTZYENKO	CNDG2_HUMAN	Decreases Expression	[32]
Coiled-coil domain-containing protein 71 (CCDC71)	OT4TJ7K8	CCD71_HUMAN	Decreases Expression	[32]
Iron-sulfur cluster co-chaperone protein HscB (HSCB)	OTP8YV25	HSC20_HUMAN	Decreases Expression	[32]
Abnormal spindle-like microcephaly-associated protein (ASPM)	OTKXQMNA	ASPM_HUMAN	Decreases Expression	[32]
EF-hand calcium-binding domain-containing protein 4A (CRACR2B)	OT8L843R	EFC4A_HUMAN	Decreases Expression	[32]
EF-hand calcium-binding domain-containing protein 3 (EFCAB3)	OT7CUMLL	EFCB3_HUMAN	Decreases Expression	[32]
Inactive phospholipase D5 (PLD5)	OTEVPYNY	PLD5_HUMAN	Increases Expression	[32]
Acyl-CoA-binding domain-containing protein 4 (ACBD4)	OTVR7MLK	ACBD4_HUMAN	Decreases Expression	[32]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Expression	[57]
Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10)	OTYKLW1K	FKB10_HUMAN	Decreases Expression	[32]
Rho-related GTP-binding protein RhoV (RHOV)	OTW4N3QN	RHOV_HUMAN	Increases Expression	[32]
Msx2-interacting protein (SPEN)	OT37A2MD	MINT_HUMAN	Increases Expression	[32]
PTB domain-containing engulfment adapter protein 1 (GULP1)	OT1WMVDH	GULP1_HUMAN	Decreases Expression	[32]
LIM/homeobox protein Lhx3 (LHX3)	OTQ5BAJ9	LHX3_HUMAN	Decreases Expression	[32]
Protein mono-ADP-ribosyltransferase PARP4 (PARP4)	OTXBK59G	PARP4_HUMAN	Decreases Expression	[32]
Ras-related protein Rab-23 (RAB23)	OTBAKFBR	RAB23_HUMAN	Decreases Expression	[32]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[48]
Sulfotransferase 4A1 (SULT4A1)	OT7AL3KJ	ST4A1_HUMAN	Increases Metabolism	[63]
Thyrotropin subunit beta (TSHB)	OTFDI39D	TSHB_HUMAN	Increases Secretion	[64]
Type I iodothyronine deiodinase (DIO1)	OTFYLYJ0	IOD1_HUMAN	Increases Chemical Synthesis	[65]
Monocarboxylate transporter 8 (SLC16A2)	OTLRA7C0	MOT8_HUMAN	Increases Uptake	[66]

References

• [1] ClinicalTrials.gov (NCT00208702) Thyroid Medication and Antidepressants for Treating Major Depression
• [2] Sertraline FDA Label
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4798).
• [4] Liothyronine FDA Label
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] ClinicalTrials.gov (NCT00790738) Liothyronine (T3) for Bipolar Depression. U.S. National Institutes of Health.
• [7] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [8] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [9] Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry. 2005 Jun;162(6):1165-70. doi: 10.1176/appi.ajp.162.6.1165.
• [10] Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein. Autophagy. 2021 Oct;17(10):2783-2799. doi: 10.1080/15548627.2020.1841953. Epub 2020 Nov 9.
• [11] Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
• [12] Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
• [13] New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients. Ther Clin Risk Manag. 2014 Jun 13;10:423-36.
• [14] The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders. CNS Drug Rev. 2001 Spring;7(1):1-24.
• [15] Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie. 2004 Jan-Feb;59(1):5-12.
• [16] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA166181117)
• [17] Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos. 2005 Feb;33(2):262-70.
• [18] Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. Int J Clin Pharm. 2016 Apr;38(2):388-94.
• [19] Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicol Lett. 2016 Jan 22;241:82-94.
• [20] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [21] Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther. 2001 Jul;70(1):42-7.
• [22] Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
• [23] Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
• [24] Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicol In Vitro. 2015 Oct;29(7):1729-35.
• [25] Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
• [26] Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies. Chem Biol Interact. 2015 Dec 5;242:235-46. doi: 10.1016/j.cbi.2015.10.006. Epub 2015 Oct 22.
• [27] Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation. 2003 Aug 26;108(8):939-44. doi: 10.1161/01.CIR.0000085163.21752.0A. Epub 2003 Aug 11.
• [28] Impact of selective serotonin reuptake inhibitors on neural crest stem cell formation. Toxicol Lett. 2017 Nov 5;281:20-25. doi: 10.1016/j.toxlet.2017.08.012. Epub 2017 Aug 24.
• [29] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [30] Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex. Neurosci Lett. 2001 Apr 6;301(3):183-6. doi: 10.1016/s0304-3940(01)01638-x.
• [31] The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology (Berl). 2004 Aug;174(4):525-9. doi: 10.1007/s00213-003-1562-3. Epub 2003 Sep 4.
• [32] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [33] Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins. Toxicology. 2010 Nov 9;277(1-3):20-8. doi: 10.1016/j.tox.2010.08.012. Epub 2010 Sep 8.
• [34] Evaluation of thyroid hormone action in a case of generalized resistance to thyroid hormone with chronic thyroiditis: discovery of a novel heterozy... Endocr J. 2007 Dec;54(5):727-32.
• [35] Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63.
• [36] Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501.
• [37] Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
• [38] LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
• [39] Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology. 2004 Sep;145(9):4384-91.
• [40] Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74.
• [41] FDA Label of Liothyronine sodium. The 2020 official website of the U.S. Food and Drug Administration.
• [42] Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate. J Endocrinol. 2001 Dec;171(3):525-32.
• [43] Thyroid hormone responsive genes in cultured human fibroblasts. J Clin Endocrinol Metab. 2005 Feb;90(2):936-43.
• [44] Negative regulation of superoxide dismutase-1 promoter by thyroid hormone. Mol Pharmacol. 2006 Sep;70(3):793-800.
• [45] Similarities and differences between two modes of antagonism of the thyroid hormone receptor. ACS Chem Biol. 2011 Oct 21;6(10):1096-106.
• [46] Activated thyroid hormone receptor modulates dioxin-inducible aryl hydrocarbon receptor-mediated CYP1A1 induction in human hepatocytes but not in human hepatocarcinoma HepG2 cells. Toxicol Lett. 2017 Jun 5;275:77-82.
• [47] Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication. J Biol Chem. 2012 Apr 20;287(17):14289-300. doi: 10.1074/jbc.M112.353201. Epub 2012 Mar 1.
• [48] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [49] Pituitary specific retinoid-X receptor ligand interactions with thyroid hormone receptor signaling revealed by high throughput reporter and endogenous gene responses. Toxicol In Vitro. 2015 Oct;29(7):1609-18. doi: 10.1016/j.tiv.2015.06.018. Epub 2015 Jun 19.
• [50] 2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor. Toxicol Appl Pharmacol. 2004 Feb 1;194(3):201-10. doi: 10.1016/j.taap.2003.09.010.
• [51] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [52] Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene. Biochem Biophys Res Commun. 1998 Aug 19;249(2):517-21. doi: 10.1006/bbrc.1998.9174.
• [53] In vitro fluorescence displacement investigation of thyroxine transport disruption by bisphenol A. J Environ Sci (China). 2011;23(2):315-21. doi: 10.1016/s1001-0742(10)60408-1.
• [54] Influence of estradiol and triiodothyronine on breast cancer cell lines proliferation and expression of estrogen and thyroid hormone receptors. Arq Bras Endocrinol Metabol. 2009 Oct;53(7):859-64. doi: 10.1590/s0004-27302009000700010.
• [55] Thyroid hormone regulates endogenous amyloid-beta precursor protein gene expression and processing in both in vitro and in vivo models. Thyroid. 2006 Dec;16(12):1207-13. doi: 10.1089/thy.2006.16.1207.
• [56] Hormonal regulation of beta2-adrenergic receptor level in prostate cancer. Prostate. 2008 Jul 1;68(10):1133-42. doi: 10.1002/pros.20778.
• [57] 3,5,3'-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis. J Cell Physiol. 2006 Feb;206(2):309-21. doi: 10.1002/jcp.20460.
• [58] Rational design and synthesis of a novel thyroid hormone antagonist that blocks coactivator recruitment. J Med Chem. 2002 Jul 18;45(15):3310-20. doi: 10.1021/jm0201013.
• [59] Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter. Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E236-45. doi: 10.1152/ajpendo.00144.2004.
• [60] Thyroid hormone regulation of prohormone convertase 1 (PC1): regional expression in rat brain and in vitro characterization of negative thyroid hormone response elements. J Mol Endocrinol. 2004 Aug;33(1):21-33. doi: 10.1677/jme.0.0330021.
• [61] Enhancement effect of resveratrol on the intestinal absorption of bestatin by regulating PEPT1, MDR1 and MRP2 in vivo and in vitro. Int J Pharm. 2015 Nov 10;495(1):588-598. doi: 10.1016/j.ijpharm.2015.09.042. Epub 2015 Sep 21.
• [62] Role of sirtuin 1 in the regulation of hepatic gene expression by thyroid hormone. J Biol Chem. 2013 Jan 11;288(2):807-18. doi: 10.1074/jbc.M112.437970. Epub 2012 Dec 3.
• [63] Highly conserved mouse and human brain sulfotransferases: molecular cloning, expression, and functional characterization. Gene. 2002 Feb 20;285(1-2):39-47. doi: 10.1016/s0378-1119(02)00431-6.
• [64] Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture. Thyroid. 2001 Feb;11(2):101-9. doi: 10.1089/105072501300042703.
• [65] Regulation of type 1 iodothyronine deiodinase in health and disease. Thyroid. 2005 Aug;15(8):835-40. doi: 10.1089/thy.2005.15.835.
• [66] Application of a nonradioactive assay for high throughput screening for inhibition of thyroid hormone uptake via the transmembrane transporter MCT8. Toxicol In Vitro. 2017 Apr;40:234-242. doi: 10.1016/j.tiv.2017.01.014. Epub 2017 Jan 21.