Identification

Name
Liotrix
Accession Number
DB01583
Type
Small Molecule
Groups
Approved
Description

Liotrix is a synthetically derived thyroid hormone replacement preparation. It consists of levothyroxine sodium (thyroxine, T4) and liothyronine sodium (triiodothyronine, T3) in a 4 to 1 ratio by weight. Liotrix was developed when it was believed that serum levels of both T4 and T3 were maintained by direct thyroidal secretion. It is now known that the thyroid gland secretes approximately ten times more T4 than T3 and that 80% of serum T3 is derived from deiodination of T4 in peripheral tissues. Administration of levothyroxine alone is sufficient for maintaining serum T4 and T3 levels in most patients and combination hormone replacement therapy generally offers no therapeutic advantage. In fact, administration of T3 may result in supratherapeutic levels of T3.

Structure
Thumb
Synonyms
  • Levothyroxine sodium - liothyronine sodium mixt
  • Liotrix (T4;T3)
International/Other Brands
Bitiron (Abdi (Turkey)) / Combithyrex (Sandoz (Austria)) / Cynoplus (Grossman (Mexico)) / Dithyron (Unipharma (Greece)) / Euthroid (Parke, Davis (United States) (discontinued)) / Euthyral (Merck-Lipha (France)) / Eutroid (Elea (Argentina)) / Levotiroxina (Farmedica (Brazil) (discontinued)) / Levotrin (GlaxoSmithKline (Argentina)) / Novothyral (Merck (Austria, Belgium, Chile, Germany, Poland, Russia, Switzerland)) / Novotiral (Merck (Mexico)) / Prothyrid (Henning (Germany), Sanofi-Aventis (Germany), Sanofi Synthelabo (Austria) (discontinued)) / Thyrolar / Tiroide Amsa (Amsa (Italy)) / Tyroplus (Enila (Brazil) (discontinued))
Categories
UNII
YW8HJ0N26X
CAS number
8065-29-0
Weight
Average: 1471.8072
Monoisotopic: 1471.440608948
Chemical Formula
C30H21I7N2Na2O8
InChI Key
LKYWLLWWYBVUPP-XOCLESOZSA-L
InChI
InChI=1S/C15H11I4NO4.C15H12I3NO4.2Na/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23;16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22;;/h1-2,4-5,12,21H,3,20H2,(H,22,23);1-4,6,12,20H,5,19H2,(H,21,22);;/q;;2*+1/p-2/t2*12-;;/m00../s1
IUPAC Name
disodium (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoate (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate
SMILES
[Na+].[Na+].N[[email protected]@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1)C([O-])=O.N[[email protected]@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C([O-])=O

Pharmacology

Indication

May be used to treat primary, secondary or tertiary hypothyroidism. May also be used to suppress thyroid stimulating hormone (TSH) secretion in patients with simple (nontoxic) goiter, subacute or chronic lymphocytic thyroiditis multinodular goiter, and in the management of thyroid cancer. May be used in conjunction with other antithyroid agents to treat thyrotoxicosis to prevent goitrogenesis and hypothyroidism. May also be used for differential diagnosis of suspected mild hyperthyroidism or thyroid gland autonomy.

Structured Indications
Not Available
Pharmacodynamics

Thyroid hormone drugs are natural or synthetic preparations containing T4 or T3 or both. T4 and T3 are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. Liotrix is a synthetic preparation of T4 and T3 in a 4:1 weight-based ratio. These hormones enhance oxygen consumption by most tissues of the body and increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system.

Mechanism of action

The hormones, T4 and T3, are tyrosine-based hormones produced by the thyroid gland. Iodine is an important component in their synthesis. The major secreted form of thyroid hormone is T4. T4 is converted T3, the more active thyroid hormone, by deiodinases in peripheral tissues. T3 acts in the body to increase basal metabolic rate, alter protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). Thyroid hormones are essential for proper development and differentiation of all cells of the human body. T4 and T3 regulate protein, fat and carbohydrate metabolism to varying extents. The most pronounced effect of the hormones is in altering how human cells use energetic compounds. The thyroid hormone derivatives bind to the thyroid hormone receptors initially to initiate their downstream effects.

TargetActionsOrganism
AThyroid hormone receptor alpha
agonist
Human
AThyroid hormone receptor beta
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Thyroid hormones are primarily eliminated by the kidneys.

Half life
Not Available
Clearance
Not Available
Toxicity

Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolLiotrix may increase the anticoagulant activities of Acenocoumarol.Approved
AfatinibThe serum concentration of Afatinib can be decreased when it is combined with Liotrix.Approved
AlaproclateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Alaproclate.Experimental
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be increased when combined with Liotrix.Experimental, Investigational
AmineptineLiotrix may increase the arrhythmogenic activities of Amineptine.Illicit, Withdrawn
AminophyllineThe metabolism of Aminophylline can be increased when combined with Liotrix.Approved
AmitriptylineLiotrix may increase the arrhythmogenic activities of Amitriptyline.Approved
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Liotrix.Approved, Investigational
AmoxapineLiotrix may increase the arrhythmogenic activities of Amoxapine.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Liotrix.Approved
Calcium AcetateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium Acetate.Approved
Calcium CarbonateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium Carbonate.Approved
Calcium ChlorideThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium Chloride.Approved
Calcium CitrateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium Citrate.Approved
Calcium glubionateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium glubionate.Approved
Calcium GluceptateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium Gluceptate.Approved
Calcium gluconateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium lactate.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium lactate gluconate.Experimental
Calcium laevulateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium laevulate.Experimental
Calcium pangamateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium pangamate.Experimental
Calcium PhosphateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Calcium Phosphate.Approved
CarbamazepineThe serum concentration of Liotrix can be decreased when it is combined with Carbamazepine.Approved, Investigational
CaseinThe therapeutic efficacy of Liotrix can be decreased when used in combination with Casein.Approved
ChlorotrianiseneThe therapeutic efficacy of Liotrix can be decreased when used in combination with Chlorotrianisene.Investigational, Withdrawn
CholestyramineThe serum concentration of Liotrix can be decreased when it is combined with Cholestyramine.Approved
CiprofloxacinThe serum concentration of Liotrix can be decreased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe therapeutic efficacy of Liotrix can be decreased when used in combination with Citalopram.Approved
ClomipramineLiotrix may increase the arrhythmogenic activities of Clomipramine.Approved, Vet Approved
ClorindioneLiotrix may increase the anticoagulant activities of Clorindione.Experimental
ColesevelamThe serum concentration of Liotrix can be decreased when it is combined with Colesevelam.Approved
ColestipolThe serum concentration of Liotrix can be decreased when it is combined with Colestipol.Approved
Conjugated estrogensThe therapeutic efficacy of Liotrix can be decreased when used in combination with Conjugated estrogens.Approved
CyclobenzaprineLiotrix may increase the arrhythmogenic activities of Cyclobenzaprine.Approved
Dabigatran etexilateThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Liotrix.Approved
DaidzeinThe therapeutic efficacy of Liotrix can be decreased when used in combination with Daidzein.Experimental
DapoxetineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Dapoxetine.Investigational
DesipramineLiotrix may increase the arrhythmogenic activities of Desipramine.Approved
DesvenlafaxineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Desvenlafaxine.Approved
DibenzepinLiotrix may increase the arrhythmogenic activities of Dibenzepin.Experimental
DicoumarolLiotrix may increase the anticoagulant activities of Dicoumarol.Approved
DienestrolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Dienestrol.Approved, Investigational
DiethylstilbestrolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Diethylstilbestrol.Approved, Investigational
DiphenadioneLiotrix may increase the anticoagulant activities of Diphenadione.Experimental
DosulepinLiotrix may increase the arrhythmogenic activities of Dosulepin.Approved
DoxepinLiotrix may increase the arrhythmogenic activities of Doxepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Liotrix.Approved, Investigational
DuloxetineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Duloxetine.Approved
DyphyllineThe metabolism of Dyphylline can be increased when combined with Liotrix.Approved
EltrombopagThe serum concentration of Liotrix can be increased when it is combined with Eltrombopag.Approved
EpimestrolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Epimestrol.Experimental
EquolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Equol.Investigational
EscitalopramThe therapeutic efficacy of Liotrix can be decreased when used in combination with Escitalopram.Approved, Investigational
EsmirtazapineLiotrix may increase the arrhythmogenic activities of Esmirtazapine.Investigational
EstradiolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Estradiol.Approved, Investigational, Vet Approved
EstriolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Estriol.Approved, Investigational, Vet Approved
Estrogens, esterifiedThe therapeutic efficacy of Liotrix can be decreased when used in combination with Estrogens, esterified.Approved
EstroneThe therapeutic efficacy of Liotrix can be decreased when used in combination with Estrone.Approved
Ethinyl EstradiolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Ethinyl Estradiol.Approved
Ethyl biscoumacetateLiotrix may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
EtoperidoneThe therapeutic efficacy of Liotrix can be decreased when used in combination with Etoperidone.Withdrawn
FluindioneLiotrix may increase the anticoagulant activities of Fluindione.Investigational
FluoxetineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Fluoxetine.Approved, Vet Approved
FluvoxamineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Fluvoxamine.Approved, Investigational
FosphenytoinThe serum concentration of Liotrix can be decreased when it is combined with Fosphenytoin.Approved
GenisteinThe therapeutic efficacy of Liotrix can be decreased when used in combination with Genistein.Investigational
HexestrolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Hexestrol.Withdrawn
ImipramineLiotrix may increase the arrhythmogenic activities of Imipramine.Approved
IndalpineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Indalpine.Investigational, Withdrawn
Iodide I-131The therapeutic efficacy of Iodide I-131 can be decreased when used in combination with Liotrix.Approved
IprindoleLiotrix may increase the arrhythmogenic activities of Iprindole.Experimental
Lanthanum carbonateThe serum concentration of Liotrix can be decreased when it is combined with Lanthanum carbonate.Approved
LedipasvirThe serum concentration of Ledipasvir can be decreased when it is combined with Liotrix.Approved
LevomilnacipranThe therapeutic efficacy of Liotrix can be decreased when used in combination with Levomilnacipran.Approved
LinagliptinThe serum concentration of Linagliptin can be decreased when it is combined with Liotrix.Approved
LofepramineLiotrix may increase the arrhythmogenic activities of Lofepramine.Experimental
MestranolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Mestranol.Approved
MethallenestrilThe therapeutic efficacy of Liotrix can be decreased when used in combination with Methallenestril.Experimental
MilnacipranThe therapeutic efficacy of Liotrix can be decreased when used in combination with Milnacipran.Approved
MirtazapineLiotrix may increase the arrhythmogenic activities of Mirtazapine.Approved
MoxestrolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Moxestrol.Experimental
NefazodoneThe therapeutic efficacy of Liotrix can be decreased when used in combination with Nefazodone.Approved, Withdrawn
NortriptylineLiotrix may increase the arrhythmogenic activities of Nortriptyline.Approved
OpipramolLiotrix may increase the arrhythmogenic activities of Opipramol.Investigational
ParoxetineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Paroxetine.Approved, Investigational
PhenindioneLiotrix may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonLiotrix may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
PhenytoinThe serum concentration of Liotrix can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PiracetamThe risk or severity of adverse effects can be increased when Piracetam is combined with Liotrix.Approved, Investigational
Polyestradiol phosphateThe therapeutic efficacy of Liotrix can be decreased when used in combination with Polyestradiol phosphate.Approved
PromestrieneThe therapeutic efficacy of Liotrix can be decreased when used in combination with Promestriene.Investigational
ProtriptylineLiotrix may increase the arrhythmogenic activities of Protriptyline.Approved
QuinestrolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Quinestrol.Approved
RifampicinThe serum concentration of Liotrix can be decreased when it is combined with Rifampicin.Approved
SecoisolariciresinolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Secoisolariciresinol.Investigational
SertralineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Sertraline.Approved
SofosbuvirThe serum concentration of Sofosbuvir can be decreased when it is combined with Liotrix.Approved
Synthetic Conjugated Estrogens, AThe therapeutic efficacy of Liotrix can be decreased when used in combination with Synthetic Conjugated Estrogens, A.Approved
Synthetic Conjugated Estrogens, BThe therapeutic efficacy of Liotrix can be decreased when used in combination with Synthetic Conjugated Estrogens, B.Approved
TeriflunomideThe serum concentration of Liotrix can be increased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Theophylline can be increased when combined with Liotrix.Approved
TianeptineLiotrix may increase the arrhythmogenic activities of Tianeptine.Approved, Investigational
TiboloneThe therapeutic efficacy of Liotrix can be decreased when used in combination with Tibolone.Approved, Investigational
TioclomarolLiotrix may increase the anticoagulant activities of Tioclomarol.Experimental
TolevamerThe serum concentration of Liotrix can be decreased when it is combined with Tolevamer.Approved
TrimipramineLiotrix may increase the arrhythmogenic activities of Trimipramine.Approved
VenlafaxineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Venlafaxine.Approved
VincristineThe serum concentration of Vincristine can be decreased when it is combined with Liotrix.Approved, Investigational
WarfarinLiotrix may increase the anticoagulant activities of Warfarin.Approved
ZeranolThe therapeutic efficacy of Liotrix can be decreased when used in combination with Zeranol.Vet Approved
ZimelidineThe therapeutic efficacy of Liotrix can be decreased when used in combination with Zimelidine.Withdrawn
Food Interactions
  • Absorption increased in fasting state and decreased in malabsorption states.
  • Consistent administration in relation to meals is recommended.
  • Iron and calcium may interfere with absorption. Space doses at least one hour before or after iron or calcium intake.
  • Oral administration with infant soybean formula, soybean flour, cotton seed meal, walnuts, foods containing large amounts of fiber, ferrous sulfate, and antacids may decrease drug absorption.
  • Take 30-60 minutes before breakfast.

References

General References
  1. Cobb WE, Jackson IM: Drug therapy reviews: management of hypothyroidism. Am J Hosp Pharm. 1978 Jan;35(1):51-8. [PubMed:341699]
External Links
Human Metabolome Database
HMDB15523
PubChem Compound
71371
PubChem Substance
46506203
ChemSpider
64467
ChEBI
6485
PharmGKB
PA164748036
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Thyrolar-3 strength tablet1.09USD tablet
Thyrolar-2 strength tablet0.89USD tablet
Thyrolar-1 strength tablet0.76USD tablet
Thyrolar-1/2 strength tablet0.61USD tablet
Thyrolar-1/4 strength tablet0.55USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP3.73ChemAxon
pKa (Strongest Acidic)0.27ChemAxon
pKa (Strongest Basic)9.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area95.61 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity137.63 m3·mol-1ChemAxon
Polarizability49.04 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9265
Blood Brain Barrier-0.5572
Caco-2 permeable-0.6254
P-glycoprotein substrateNon-substrate0.5404
P-glycoprotein inhibitor INon-inhibitor0.9229
P-glycoprotein inhibitor IINon-inhibitor0.9089
Renal organic cation transporterNon-inhibitor0.8928
CYP450 2C9 substrateNon-substrate0.8097
CYP450 2D6 substrateNon-substrate0.878
CYP450 3A4 substrateNon-substrate0.7092
CYP450 1A2 substrateNon-inhibitor0.5872
CYP450 2C9 inhibitorNon-inhibitor0.6523
CYP450 2D6 inhibitorNon-inhibitor0.8638
CYP450 2C19 inhibitorNon-inhibitor0.8585
CYP450 3A4 inhibitorNon-inhibitor0.8711
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8243
Ames testNon AMES toxic0.763
CarcinogenicityNon-carcinogens0.8526
BiodegradationNot ready biodegradable0.9697
Rat acute toxicity2.5191 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9672
hERG inhibition (predictor II)Non-inhibitor0.8731
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
Diphenylethers / Phenylpropanoic acids / Diarylethers / L-alpha-amino acids / Amphetamines and derivatives / Phenoxy compounds / Phenol ethers / O-iodophenols / Phenoxides / 1-hydroxy-2-unsubstituted benzenoids
show 16 more
Substituents
Phenylalanine or derivatives / Diphenylether / Diaryl ether / 3-phenylpropanoic-acid / Alpha-amino acid / Amphetamine or derivatives / L-alpha-amino acid / Phenoxy compound / 2-halophenol / 2-iodophenol
show 35 more
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Al...
Gene Name
THRA
Uniprot ID
P10827
Uniprot Name
Thyroid hormone receptor alpha
Molecular Weight
54815.055 Da
References
  1. Jiang W, Miyamoto T, Kakizawa T, Sakuma T, Nishio S, Takeda T, Suzuki S, Hashizume K: Expression of thyroid hormone receptor alpha in 3T3-L1 adipocytes; triiodothyronine increases the expression of lipogenic enzyme and triglyceride accumulation. J Endocrinol. 2004 Aug;182(2):295-302. [PubMed:15283690]
  2. Kariv R, Enden A, Zvibel I, Rosner G, Brill S, Shafritz DA, Halpern Z, Oren R: Triiodothyronine and interleukin-6 (IL-6) induce expression of HGF in an immortalized rat hepatic stellate cell line. Liver Int. 2003 Jun;23(3):187-93. [PubMed:12955882]
  3. Mai W, Janier MF, Allioli N, Quignodon L, Chuzel T, Flamant F, Samarut J: Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10332-7. Epub 2004 Jul 6. [PubMed:15240882]
  4. Sciaudone MP, Yao L, Schaller M, Zinn SA, Freake HC: Diethylenetriaminepentaacetic acid enhances thyroid hormone action by a transcriptional mechanism. Biol Trace Elem Res. 2004 Summer;99(1-3):219-31. [PubMed:15235154]
  5. Timmer DC, Bakker O, Wiersinga WM: Triiodothyronine affects the alternative splicing of thyroid hormone receptor alpha mRNA. J Endocrinol. 2003 Nov;179(2):217-25. [PubMed:14596673]
  6. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. [PubMed:17315033]
  7. Nakajima Y, Yamada M, Horiguchi K, Satoh T, Hashimoto K, Tokuhiro E, Onigata K, Mori M: Resistance to thyroid hormone due to a novel thyroid hormone receptor mutant in a patient with hypothyroidism secondary to lingual thyroid and functional characterization of the mutant receptor. Thyroid. 2010 Aug;20(8):917-26. doi: 10.1089/thy.2009.0389. [PubMed:20615127]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  9. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  10. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
Gene Name
THRB
Uniprot ID
P10828
Uniprot Name
Thyroid hormone receptor beta
Molecular Weight
52787.16 Da
References
  1. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. [PubMed:17315033]
  2. Gonzalez-Sancho JM, Garcia V, Bonilla F, Munoz A: Thyroid hormone receptors/THR genes in human cancer. Cancer Lett. 2003 Mar 31;192(2):121-32. [PubMed:12668276]
  3. Yen PM, Feng X, Flamant F, Chen Y, Walker RL, Weiss RE, Chassande O, Samarut J, Refetoff S, Meltzer PS: Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice. EMBO Rep. 2003 Jun;4(6):581-7. [PubMed:12776178]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  5. Wu SY, Sadow PM, Refetoff S, Weiss RE: Tissue responses to thyroid hormone in a kindred with resistance to thyroid hormone harboring a commonly occurring mutation in the thyroid hormone receptor beta gene (P453T). J Lab Clin Med. 2005 Aug;146(2):85-94. [PubMed:16099238]
  6. Marazuela M, Nattero L, Moure D, Garcia-Polo I, Figueroa-Vega N, Guijarro C: Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23. doi: 10.1089/thy.2007.0375. [PubMed:18816177]
  7. Sivakumar T, Chaidarun S: Resistance to thyroid hormone in a patient with coexisting Graves' disease. Thyroid. 2010 Feb;20(2):213-6. doi: 10.1089/thy.2009.0175. [PubMed:20151830]
  8. Grasberger H, Ringkananont U, Croxson M, Refetoff S: Resistance to thyroid hormone in a patient with thyroid dysgenesis. Thyroid. 2005 Jul;15(7):730-3. [PubMed:16053391]
  9. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  10. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Identical protein binding
Specific Function
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Gene Name
TTR
Uniprot ID
P02766
Uniprot Name
Transthyretin
Molecular Weight
15886.88 Da
References
  1. Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AE: High resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxine. J Biol Chem. 2004 Jun 18;279(25):26411-6. Epub 2004 Apr 13. [PubMed:15082720]
  2. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [PubMed:12553433]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [PubMed:12553433]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [PubMed:12553433]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Fujiwara K, Adachi H, Nishio T, Unno M, Tokui T, Okabe M, Onogawa T, Suzuki T, Asano N, Tanemoto M, Seki M, Shiiba K, Suzuki M, Kondo Y, Nunoki K, Shimosegawa T, Iinuma K, Ito S, Matsuno S, Abe T: Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12. [PubMed:11316767]
  2. Friesema EC, Docter R, Moerings EP, Stieger B, Hagenbuch B, Meier PJ, Krenning EP, Hennemann G, Visser TJ: Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501. [PubMed:9918867]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Abe T, Kakyo M, Tokui T, Nakagomi R, Nishio T, Nakai D, Nomura H, Unno M, Suzuki M, Naitoh T, Matsuno S, Yawo H: 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. [PubMed:10358072]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
  2. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma K, Nagura H, Ito S, Matsuno S: LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. [PubMed:11375950]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ...
Gene Name
SLCO4C1
Uniprot ID
Q6ZQN7
Uniprot Name
Solute carrier organic anion transporter family member 4C1
Molecular Weight
78947.525 Da
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: 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. Epub 2004 Mar 1. [PubMed:14993604]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Friesema EC, Docter R, Moerings EP, Stieger B, Hagenbuch B, Meier PJ, Krenning EP, Hennemann G, Visser TJ: Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501. [PubMed:9918867]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-gluc...
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
References
  1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. doi: 10.1210/en.2008-0188. Epub 2008 Oct 9. [PubMed:18845642]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  3. Tohyama K, Kusuhara H, Sugiyama Y: 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. Epub 2004 May 27. [PubMed:15166123]
  4. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [PubMed:12351693]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate.
Gene Name
SLCO4A1
Uniprot ID
Q96BD0
Uniprot Name
Solute carrier organic anion transporter family member 4A1
Molecular Weight
77192.505 Da
References
  1. Fujiwara K, Adachi H, Nishio T, Unno M, Tokui T, Okabe M, Onogawa T, Suzuki T, Asano N, Tanemoto M, Seki M, Shiiba K, Suzuki M, Kondo Y, Nunoki K, Shimosegawa T, Iinuma K, Ito S, Matsuno S, Abe T: Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12. [PubMed:11316767]
  2. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: 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. Epub 2004 Mar 1. [PubMed:14993604]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [PubMed:14762099]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Very active and specific thyroid hormone transporter. Stimulates cellular uptake of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine. Does not transport Leu,...
Gene Name
SLC16A2
Uniprot ID
P36021
Uniprot Name
Monocarboxylate transporter 8
Molecular Weight
59510.86 Da
References
  1. Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ: Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem. 2003 Oct 10;278(41):40128-35. Epub 2003 Jul 18. [PubMed:12871948]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells (By similarity).
Gene Name
SLC16A10
Uniprot ID
Q8TF71
Uniprot Name
Monocarboxylate transporter 10
Molecular Weight
55492.07 Da
References
  1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. [PubMed:11278508]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Siegmund W, Altmannsberger S, Paneitz A, Hecker U, Zschiesche M, Franke G, Meng W, Warzok R, Schroeder E, Sperker B, Terhaag B, Cascorbi I, Kroemer HK: Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition. Clin Pharmacol Ther. 2002 Sep;72(3):256-64. [PubMed:12235446]
  2. Ashida K, Katsura T, Motohashi H, Saito H, Inui K: Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G617-23. [PubMed:11897620]

Drug created on August 29, 2007 08:54 / Updated on November 09, 2017 03:02