Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMHN027)

Drug Name
Levothyroxine Drug Info
Synonyms
Eltroxin; Euthyrox; Forthyron; Laevothyroxinum; Laevoxin; Levolet; Levothroid; Levothyrox; Levothyroxin; Levoxyl; Oroxine; Synthroid; THX; Tetraiodothyronine; Thyratabs; Thyrax; Thyreoideum; Thyroxevan; Thyroxin; Thyroxinal; Levothyroxine sodium; Synthroid sodium; Thyroxine [BAN]; Thyroxine iodine; LT00440967; T4 levothyroxine; DL-Thyroxin; Eltroxin (TN); Euthyrox (TN); Eutirox (TN); Forthyron (TN); L-Thryoxin; L-Thyroxin; L-thyroxine; Laevothyroxinum (acid); Levaxin (TN); Levo-T; Levothyroxine (BAN); Levothyroxinum (acid); Levoxyl (TN); Synthroid (TN); T-3850; T4 (Hormone); Thyrax (TN); Thyrox (TN); Thyroxine (VAN); Thyroxine (l); L-thyroxine (TN); Levothyroxine Sodium (L-thyroxine); Levothroid (*Sodiumsalt*); Synthroid (*Sodium salt*); Thyroxine, L-(8CI); L-3,5,3',5'-Tetraiodothyronine; O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodotyrosine; Beta-((3,5-Diiodo-4-hydroxyphenoxy)-3,5-diiodophenyl)alanine; O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine; O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine; (-)-Thyroxine; (125I)T4; (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid; 2-amino-3-[4-(4-hydroxy-3,5-diiodo-phenoxy)-3,5-diiodo-phenyl]-propanoic acid; 3,3',5,5"-Tetraiodo-L-thyronine; 3,3',5,5''-Tetraiodo-L-thyronine; 3,3',5,5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodothyronine; 3,5,3'5'-Tetraiodo-L-thyronine; 3-(4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)alanine; 3-[4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine; 4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodo-L-phenylalanine
Indication
Disease Entry ICD 11 Status REF
Congenital hypothyroidism Approved [1]
Edema MG29 Approved [1]
Goiter Approved [1]
Hashimoto thyroiditis Approved [1]
Hyperlipidemia 5C80.Z Approved [1]
Hypothyroidism 5A00 Approved [2]
Thyroid cancer 2D10 Approved [1]
Therapeutic Class
Antithyroid Agents
Cross-matching ID
PubChem CID
5819
ChEBI ID
CHEBI:18332
CAS Number
CAS 51-48-9
TTD Drug ID
DMHN027
VARIDT Drug ID
DR00107
INTEDE Drug ID
DR0948

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DME
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Investigative Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Thyroid hormone receptor alpha (THRA)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Liothyronine DM6IR3P Congenital hypothyroidism Approved [9]
Dextrothyroxine Sodium DMBVEC7 High blood cholesterol level 5C80.00 Approved [10]
BCT303 DMUFY4K Hypothyroidism 5A00 Phase 2 [11]
tiratricol DMZO6CV Wound healing EL8Y Clinical trial [12]
3-(dibutylamino)-1-(4-hexylphenyl)propan-1-one DM2JBQI Discovery agent N.A. Investigative [13]
3-(3,5-Dibromo-4-hexyloxy-phenyl)-propionic acid DMDFHCU Discovery agent N.A. Investigative [14]
3-(dimethylamino)-1-(4-hexylphenyl)propan-1-one DMJYCHG Discovery agent N.A. Investigative [13]
4-(4-hexylphenyl)-4-oxobut-2-enoic acid DMR9TBW Discovery agent N.A. Investigative [13]
(3,5-Dibromo-4-hexyloxy-phenyl)-acetic acid DM5GN46 Discovery agent N.A. Investigative [14]
1-(4-hexylphenyl)-3-morpholinopropan-1-one DMFN8T6 Discovery agent N.A. Investigative [13]
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Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL Anterior urethra cancer Approved [15]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [16]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [17]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [18]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [17]
Pravastatin DM6A0X7 Adult acute monocytic leukemia Approved [19]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [20]
Atorvastatin DMF28YC Acute coronary syndrome BA41 Approved [21]
Cerivastatin DMXCM7H Hyperlipidaemia 5C80 Approved [22]
PITAVASTATIN CALCIUM DM1UJO0 Dyslipidemia 5C80-5C81 Approved [19]
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Drug(s) Transported By Organic anion transporting polypeptide 1A2 (SLCO1A2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL Anterior urethra cancer Approved [23]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [24]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [25]
Atorvastatin DMF28YC Acute coronary syndrome BA41 Approved [26]
PITAVASTATIN CALCIUM DM1UJO0 Dyslipidemia 5C80-5C81 Approved [27]
Rosuvastatin DMMIQ7G Arteriosclerosis BD40 Approved [28]
Saquinavir DMG814N Human immunodeficiency virus infection 1C62 Approved [29]
Enalapril DMNFUZR Congestive heart failure BD10 Approved [30]
Cholic Acid DM7OKQV Cholelithiasis DC11 Approved [31]
Liothyronine DM6IR3P Congenital hypothyroidism Approved [5]
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Drug(s) Transported By Organic anion transporting polypeptide 1C1 (SLCO1C1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [4]
Liothyronine DM6IR3P Congenital hypothyroidism Approved [32]
[3H]estradiol-17beta-glucuronide DM3KJ45 Discovery agent N.A. Investigative [33]
Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [34]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [35]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [36]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [37]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [38]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [39]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [40]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [41]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [35]
Verapamil DMA7PEW Angina pectoris BA40 Approved [42]
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Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [43]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [44]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [45]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [46]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [47]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [48]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [49]
Metronidazole DMTIVEN Abscess Approved [8]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [50]
Ethanol DMDRQZU Chronic pain MG30 Approved [51]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Thyroid hormone receptor alpha (THRA) TTTSEPU THA_HUMAN Antagonist [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1C1 (SLCO1C1) DTPYCQ4 SO1C1_HUMAN Substrate [4]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [5]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [8]

References

1 Levothyroxine FDA Label
2 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).
3 Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23.
4 Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96.
5 Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
6 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.
7 [Metabolic interaction between psychopharmaceuticals. Probable cause of exacerbation of hypothyroidism according to a case report]. Lakartidningen. 2002 Jun 20;99(25):2854-6.
8 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.
9 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.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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12 Binding of 3,5,3'-triiodothyronine (T3) and its analogs to the in vitro translational products of c-erbA protooncogenes: differences in the affinity of the alpha- and beta-forms for the acetic acid analog and failure of the human testis and kidney alpha-2 products to bind T3. Mol Endocrinol. 1990 Feb;4(2):227-34.
13 Inhibitors of the interaction of a thyroid hormone receptor and coactivators: preliminary structure-activity relationships. J Med Chem. 2007 Nov 1;50(22):5269-80.
14 Thyroid receptor ligands. 3. Design and synthesis of 3,5-dihalo-4-alkoxyphenylalkanoic acids as indirect antagonists of the thyroid hormone receptor. J Med Chem. 2005 May 5;48(9):3114-7.
15 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
16 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
17 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
18 Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
19 The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
20 Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
21 Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
22 FDA Drug Development and Drug Interactions
23 Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
24 Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95.
25 Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
26 Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
27 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
28 Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
29 Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm. 2004 Jan 12;1(1):49-56.
30 Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6.
31 Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
32 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.
33 The blood-brain barrier thyroxine transporter organic anion-transporting polypeptide 1c1 displays atypical transport kinetics. Endocrinology. 2009 Nov;150(11):5153-62.
34 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
35 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
36 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
37 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
38 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
39 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
40 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
41 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
42 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
43 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
44 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
45 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
46 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
47 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
48 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
49 Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
50 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
51 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.