Dextrothyroxine

Identification

Summary

Dextrothyroxine is a thyroid hormone used to treat hyperlipidemia.

Generic Name
Dextrothyroxine
DrugBank Accession Number
DB00509
Background

The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 776.87
Monoisotopic: 776.686681525
Chemical Formula
C15H11I4NO4
Synonyms
  • D-thyroxine
  • Dextrothyroxine
  • Dextrothyroxinum
  • O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-D-tyrosine

Pharmacology

Indication

Used to lower high cholesterol levels in the blood.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Dextrothyroxine, the dextrorotary isomer of the synthetic thyroxine, is a antihyperlipidemic.

Mechanism of action

Dextrothyroxine is a antihyperlipidemic. The mechanism of action is not completely understood, but dextrothyroxine apparently acts in the liver to stimulate formation of low-density lipoprotein (LDL) and, to a much greater extent, to increase catabolism of LDL. This leads to increased excretion of cholesterol and bile acids via the biliary route into the feces, with a resulting reduction in serum cholesterol and LDL. Dextrothyroxine has no significant effect on high-density lipoproteins (HDL). Inherently, it will also bind to thyroid receptors and as it is a prohormone, it will bind as a substrate to iodide peroxidase.

TargetActionsOrganism
AThyroid hormone receptor alpha
agonist
Humans
AThyroid hormone receptor beta
agonist
Humans
UThyroid peroxidaseNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hover over products below to view reaction partners

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of dextrothyroxine overdose are unknown.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Dextrothyroxine sodium0H00N2AHSP7054-08-2ANMYAHDLKVNJJO-CURYUGHLSA-M
International/Other Brands
Choloxin (Knoll (Canada) (discontinued), Baxter (United Kingdom) (discontinued), Boots-Flint (United States) (discontinued)) / Dynothel (Henning (Germany) (discontinued)) / Eulipos (Boehringer Mannheim (Germany) (discontinued)) / Lisolipin (Bracco (Italy) (discontinued))
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Choloxin - Tab 4mgTablet4 mg / tabOralKnoll Pharma Inc.1996-12-311999-12-31Canada flag
Choloxin Tab 2mgTablet2 mg / tabOralBoots Pharmaceuticals Ltd.1973-12-311996-09-09Canada flag
Choloxin Tab 2mgTablet2 mg / tabOralKnoll Pharma Inc.1996-12-311999-12-31Canada flag
Choloxin Tablet 4mgTablet4 mg / tabOralBoots Pharmaceuticals Ltd.1960-12-311996-09-09Canada flag

Categories

ATC Codes
C10AX01 — Dextrothyroxine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / Amphetamines and derivatives / D-alpha-amino acids / Phenoxy compounds / Phenol ethers / O-iodophenols / Aralkylamines / Iodobenzenes
show 10 more
Substituents
2-halophenol / 2-iodophenol / 3-phenylpropanoic-acid / Alpha-amino acid / Amine / Amino acid / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound / Aryl halide
show 27 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
thyroxine, D-tyrosine derivative (CHEBI:30659)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4W9K63FION
CAS number
51-49-0
InChI Key
XUIIKFGFIJCVMT-GFCCVEGCSA-N
InChI
InChI=1S/C15H11I4NO4/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/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m1/s1
IUPAC Name
(2R)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
SMILES
N[C@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O

References

General References
  1. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37. [Article]
Human Metabolome Database
HMDB0014651
PubChem Compound
8730
PubChem Substance
46508471
ChemSpider
8402
BindingDB
50225220
RxNav
3292
ChEBI
30659
ChEMBL
CHEMBL559
ZINC
ZINC000003830994
PharmGKB
PA164752444
Wikipedia
Dextrothyroxine
MSDS
Download (60.6 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral2 mg / tab
TabletOral4 mg / tab
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)235-236 °CNot Available
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00898 mg/mLALOGPS
logP1.15ALOGPS
logP3.73Chemaxon
logS-4.9ALOGPS
pKa (Strongest Acidic)0.27Chemaxon
pKa (Strongest Basic)9.43Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area92.78 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity126.79 m3·mol-1Chemaxon
Polarizability49.38 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7212
Blood Brain Barrier-0.6886
Caco-2 permeable-0.653
P-glycoprotein substrateNon-substrate0.5321
P-glycoprotein inhibitor INon-inhibitor0.9175
P-glycoprotein inhibitor IINon-inhibitor0.9709
Renal organic cation transporterNon-inhibitor0.8891
CYP450 2C9 substrateNon-substrate0.8309
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6847
CYP450 1A2 substrateNon-inhibitor0.5924
CYP450 2C9 inhibitorNon-inhibitor0.7037
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8459
Ames testNon AMES toxic0.7591
CarcinogenicityNon-carcinogens0.9148
BiodegradationNot ready biodegradable0.9693
Rat acute toxicity2.7082 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9697
hERG inhibition (predictor II)Non-inhibitor0.8508
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0f89-4002002900-0d489fed1cb888a2d9d0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-003r-0000000900-6e0459f5e77984b3fda5
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0000000900-8d1289fe69268614c044
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03e9-0000000900-d43f6ed14d6b30069177
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ue9-0000005900-066942eb510fca0168da
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-1901006700-5eaab94a5f9fc2b7763b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0901000300-8fc21cc9818781442f33
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-188.9128872
predicted
DarkChem Lite v0.1.0
[M-H]-188.9434872
predicted
DarkChem Lite v0.1.0
[M-H]-214.99162
predicted
DeepCCS 1.0 (2019)
[M+H]+189.1796872
predicted
DarkChem Lite v0.1.0
[M+H]+217.54193
predicted
DeepCCS 1.0 (2019)
[M+Na]+189.0042872
predicted
DarkChem Lite v0.1.0
[M+Na]+224.56264
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  3. 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. [Article]
  4. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  5. 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. [Article]
  6. 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. [Article]
  7. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Peroxidase activity
Specific Function
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Gene Name
TPO
Uniprot ID
P07202
Uniprot Name
Thyroid peroxidase
Molecular Weight
102961.63 Da
References
  1. Visser TJ: The elemental importance of sufficient iodine intake: a trace is not enough. Endocrinology. 2006 May;147(5):2095-7. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Peptide antigen binding
Specific Function
Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular a...
Gene Name
SLC7A5
Uniprot ID
Q01650
Uniprot Name
Large neutral amino acids transporter small subunit 1
Molecular Weight
55009.62 Da
References
  1. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 02:27