Details of the Drug Combination

General Information of Drug Combination (ID: DCS5BIQ)

Drug Combination Name
Liothyronine Levothyroxine
Indication
Disease Entry Status REF
Thyroid Goiter Phase 2 [1]
Component Drugs Liothyronine   DM6IR3P Levothyroxine   DMHN027
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [9]
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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 [10]
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DT56EKP NTCP_HUMAN Substrate [11]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [12]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [13]
Organic anion transporting polypeptide 1C1 (SLCO1C1) DTPYCQ4 SO1C1_HUMAN Substrate [14]
Organic anion transporting polypeptide 4A1 (SLCO4A1) DT8H2IC SO4A1_HUMAN Substrate [15]
Organic anion transporting polypeptide 4C1 (SLCO4C1) DTY0QMU SO4C1_HUMAN Substrate [15]
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⏷ Show the Full List of 7 DTP(s)
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 [16]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [17]
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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 [17]
Monocarboxylate transporter 4 (SLC16A3) OTDIXEXY MOT4_HUMAN Increases Expression [18]
All-trans-retinol dehydrogenase ADH1B (ADH1B) OTV3TB81 ADH1B_HUMAN Decreases Expression [18]
Alpha-enolase (ENO1) OTB1KWJS ENOA_HUMAN Increases Expression [18]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Increases Expression [18]
Collagen alpha-3(VI) chain (COL6A3) OTAS6R6I CO6A3_HUMAN Increases Expression [18]
Ras-related protein Rab-3B (RAB3B) OTZA4SXL RAB3B_HUMAN Increases Expression [18]
Fibroblast growth factor 7 (FGF7) OTGK6ANL FGF7_HUMAN Decreases Expression [18]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Increases Expression [18]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Increases Expression [18]
ATP-dependent 6-phosphofructokinase, platelet type (PFKP) OTFP7AA8 PFKAP_HUMAN Increases Expression [18]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Increases Expression [18]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [18]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Decreases Expression [19]
Monocarboxylate transporter 7 (SLC16A6) OT7BIIZX MOT7_HUMAN Increases Expression [20]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [20]
Stromelysin-3 (MMP11) OTRTXDBM MMP11_HUMAN Increases Expression [20]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1) OTNWEJ5Y PCKGC_HUMAN Increases Expression [20]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1) OTJ6FM9F G6PC1_HUMAN Increases Expression [20]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Increases Expression [20]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [20]
Transcriptional and immune response regulator (TCIM) OTARUXQF TCIM_HUMAN Increases Expression [20]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [21]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [21]
Thyroid hormone-inducible hepatic protein (THRSP) OTKYE01L THRSP_HUMAN Increases Expression [21]
Uncharacterized protein C20orf204 (C20ORF204) OT0GVQPP CT204_HUMAN Decreases Expression [7]
Meiosis-specific coiled-coil domain-containing protein MEIOC (MEIOC) OTME1FFG MEIOC_HUMAN Decreases Expression [7]
LYR motif-containing protein 9 (LYRM9) OT1MILTK LYRM9_HUMAN Decreases Expression [7]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Phosphorylation [22]
Apolipoprotein L1 (APOL1) OT8QBVTY APOL1_HUMAN Decreases Expression [7]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [23]
Serine palmitoyltransferase 2 (SPTLC2) OTBTMH1Z SPTC2_HUMAN Increases Expression [7]
Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) OTZKOTDB ADA12_HUMAN Increases Expression [7]
Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2) OTR7WJES DC1L2_HUMAN Increases Expression [7]
Trans-Golgi network integral membrane protein 2 (TGOLN2) OTM647IV TGON2_HUMAN Decreases Expression [7]
Lysine-specific demethylase hairless (HR) OTHEZWPW HAIR_HUMAN Increases Expression [24]
Prostate stem cell antigen (PSCA) OTQ574EY PSCA_HUMAN Increases Expression [25]
Plexin-C1 (PLXNC1) OTJ5XKYY PLXC1_HUMAN Increases Expression [7]
TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L) OTCP6ZYD TAF5L_HUMAN Increases Expression [7]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [26]
Echinoderm microtubule-associated protein-like 2 (EML2) OTRX2NTA EMAL2_HUMAN Increases Expression [7]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Increases Expression [27]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [23]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [23]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [28]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [29]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [23]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Decreases Expression [30]
Thyroxine-binding globulin (SERPINA7) OTUYVTSU THBG_HUMAN Affects Binding [8]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Expression [31]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) OTXOQDSG IFIT1_HUMAN Decreases Expression [7]
Histone H2A type 1 (H2AC11) OTN9P0BO H2A1_HUMAN Decreases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [23]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [32]
Thyroid hormone receptor beta (THRB) OTBBIRHZ THB_HUMAN Increases Expression [33]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Affects Binding [22]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Increases Expression [25]
Replication protein A 32 kDa subunit (RPA2) OTZ54WAF RFA2_HUMAN Increases Phosphorylation [22]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [22]
Histone H1.5 (H1-5) OTAN7RD9 H15_HUMAN Increases Expression [7]
Neuroendocrine convertase 2 (PCSK2) OT9Y2Z9B NEC2_HUMAN Decreases Expression [34]
Integrin beta-5 (ITGB5) OT21MF51 ITB5_HUMAN Decreases Expression [7]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Increases Expression [32]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [26]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Decreases Expression [25]
Interleukin-32 (IL32) OT3FHZ81 IL32_HUMAN Increases Expression [25]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Expression [32]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Increases Expression [32]
Neuroendocrine convertase 1 (PCSK1) OTPBRJ54 NEC1_HUMAN Decreases Expression [35]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [32]
Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3) OTODTW0I HNRH3_HUMAN Increases Expression [7]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [23]
Beta-adducin (ADD2) OTRCPCD2 ADDB_HUMAN Increases Expression [7]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [25]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [32]
Solute carrier family 15 member 1 (SLC15A1) OT1P16B5 S15A1_HUMAN Decreases Expression [36]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Decreases Expression [32]
Inactive serine/threonine-protein kinase 19 (STK19) OTYM6437 STK19_HUMAN Increases Expression [7]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Increases Expression [37]
Peroxisomal targeting signal 1 receptor (PEX5) OTK4LMG7 PEX5_HUMAN Increases Expression [7]
Protein HIRA (HIRA) OTON40EJ HIRA_HUMAN Increases Expression [7]
Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2) OTC3RUN9 HMCS2_HUMAN Increases Expression [7]
Thyroxine 5-deiodinase (DIO3) OTNTITOT IOD3_HUMAN Increases Expression [7]
A-kinase anchor protein 12 (AKAP12) OTCVRDDX AKA12_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 2 (DUSP2) OTH54FMR DUS2_HUMAN Decreases Expression [25]
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) OTNOM26L TNR9_HUMAN Increases Expression [25]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [32]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [32]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [23]
Pregnancy-specific beta-1-glycoprotein 7 (PSG7) OT1IXGBX PSG7_HUMAN Increases Expression [25]
TNF receptor-associated factor 1 (TRAF1) OTTLM5RU TRAF1_HUMAN Increases Expression [25]
Disintegrin and metalloproteinase domain-containing protein 15 (ADAM15) OTZ7VLTP ADA15_HUMAN Decreases Expression [7]
Krueppel-like factor 9 (KLF9) OTBFEJRQ KLF9_HUMAN Decreases Expression [7]
Glutamate receptor ionotropic, kainate 4 (GRIK4) OTL5EIPA GRIK4_HUMAN Increases Expression [7]
kinase isozyme 4, mitochondrial (PDK4) OTCMHMBZ PDK4_HUMAN Increases Expression [37]
Tigger transposable element-derived protein 6 (TIGD6) OT8S6ZQW TIGD6_HUMAN Increases Expression [7]
Transmembrane protein 44 (TMEM44) OTRUF467 TMM44_HUMAN Increases Expression [7]
Akirin-2 (AKIRIN2) OTQ6WSKW AKIR2_HUMAN Increases Expression [7]
Protein FAM171B (FAM171B) OT4DJHCM F171B_HUMAN Decreases Expression [7]
Protein FAM83H (FAM83H) OTN0SF11 FA83H_HUMAN Increases Expression [7]
Butyrophilin subfamily 2 member A1 (BTN2A1) OTUYPMZJ BT2A1_HUMAN Decreases Expression [7]
Mesoderm induction early response protein 3 (MIER3) OTL5BGOB MIER3_HUMAN Decreases Expression [7]
Tripartite motif-containing protein 46 (TRIM46) OTFE7WZW TRI46_HUMAN Increases Expression [7]
Retrotransposon-derived protein PEG10 (PEG10) OTWD2278 PEG10_HUMAN Increases Expression [7]
Rho guanine nucleotide exchange factor 25 (ARHGEF25) OT7162TD ARHGP_HUMAN Decreases Expression [7]
Condensin-2 complex subunit G2 (NCAPG2) OTZYENKO CNDG2_HUMAN Decreases Expression [7]
Coiled-coil domain-containing protein 71 (CCDC71) OT4TJ7K8 CCD71_HUMAN Decreases Expression [7]
Iron-sulfur cluster co-chaperone protein HscB (HSCB) OTP8YV25 HSC20_HUMAN Decreases Expression [7]
Abnormal spindle-like microcephaly-associated protein (ASPM) OTKXQMNA ASPM_HUMAN Decreases Expression [7]
EF-hand calcium-binding domain-containing protein 4A (CRACR2B) OT8L843R EFC4A_HUMAN Decreases Expression [7]
EF-hand calcium-binding domain-containing protein 3 (EFCAB3) OT7CUMLL EFCB3_HUMAN Decreases Expression [7]
Inactive phospholipase D5 (PLD5) OTEVPYNY PLD5_HUMAN Increases Expression [7]
Acyl-CoA-binding domain-containing protein 4 (ACBD4) OTVR7MLK ACBD4_HUMAN Decreases Expression [7]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Decreases Expression [32]
Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10) OTYKLW1K FKB10_HUMAN Decreases Expression [7]
Rho-related GTP-binding protein RhoV (RHOV) OTW4N3QN RHOV_HUMAN Increases Expression [7]
Msx2-interacting protein (SPEN) OT37A2MD MINT_HUMAN Increases Expression [7]
PTB domain-containing engulfment adapter protein 1 (GULP1) OT1WMVDH GULP1_HUMAN Decreases Expression [7]
LIM/homeobox protein Lhx3 (LHX3) OTQ5BAJ9 LHX3_HUMAN Decreases Expression [7]
Protein mono-ADP-ribosyltransferase PARP4 (PARP4) OTXBK59G PARP4_HUMAN Decreases Expression [7]
Ras-related protein Rab-23 (RAB23) OTBAKFBR RAB23_HUMAN Decreases Expression [7]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [23]
Sulfotransferase 4A1 (SULT4A1) OT7AL3KJ ST4A1_HUMAN Increases Metabolism [38]
Thyrotropin subunit beta (TSHB) OTFDI39D TSHB_HUMAN Increases Secretion [39]
Type I iodothyronine deiodinase (DIO1) OTFYLYJ0 IOD1_HUMAN Increases Chemical Synthesis [40]
Monocarboxylate transporter 8 (SLC16A2) OTLRA7C0 MOT8_HUMAN Increases Uptake [41]
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⏷ Show the Full List of 126 DOT(s)
Indication(s) of Levothyroxine
Disease Entry ICD 11 Status REF
Congenital hypothyroidism N.A. Approved [5]
Edema MG29 Approved [5]
Goiter N.A. Approved [5]
Hashimoto thyroiditis N.A. Approved [5]
Hyperlipidemia 5C80.Z Approved [5]
Hypothyroidism 5A00 Approved [6]
Thyroid cancer 2D10 Approved [5]
Levothyroxine 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 [42]
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Levothyroxine Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [10]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [12]
Organic anion transporting polypeptide 1C1 (SLCO1C1) DTPYCQ4 SO1C1_HUMAN Substrate [43]
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Levothyroxine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [44]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [45]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hypothyroidism DC3GBOE N. A. Phase 1 [46]
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References

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2 Liothyronine FDA Label
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5 Levothyroxine FDA Label
6 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: 4627).
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13 LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
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19 Negative regulation of superoxide dismutase-1 promoter by thyroid hormone. Mol Pharmacol. 2006 Sep;70(3):793-800.
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35 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.
36 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.
37 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.
38 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.
39 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.
40 Regulation of type 1 iodothyronine deiodinase in health and disease. Thyroid. 2005 Aug;15(8):835-40. doi: 10.1089/thy.2005.15.835.
41 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.
42 Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23.
43 Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96.
44 [Metabolic interaction between psychopharmaceuticals. Probable cause of exacerbation of hypothyroidism according to a case report]. Lakartidningen. 2002 Jun 20;99(25):2854-6.
45 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
46 ClinicalTrials.gov (NCT00488644) Combined Levothyroxine/Liothyronine Supplementation in Hypothyroid Patients With Brain Tumors