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Identification
Name Dextrothyroxine
Accession Number DB00509 (APRD00911)
Type small molecule
Groups approved
Description

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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 3,5,3′,5′-Tetraiodo-d-thyronine Sodium
  • D-Thyroxine Sodium
  • Dekstrotyroksiininatrium
  • Dextrothyroxinum Natricum
  • Dextrotiroxina sódica
  • Dextrotyroxinnatrium
  • Sodium 4-O-(4-hydroxy-3,5-di-iodophenyl)-3,5-di-iodo-d-tyrosinate hydrate
Brand names
  • 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 mixtures Not Available
Categories
  • Antihyperlipidemics
CAS number 51-49-0
Weight Average: 776.87
Monoisotopic: 776.686681525
Chemical Formula C15H11I4NO4
InChI Key InChIKey=XUIIKFGFIJCVMT-UHFFFAOYSA-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)
Plain Text
IUPAC Name
2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
SMILES
NC(CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Methoxyphenols
  • Phenethylamines
  • Amphetamines
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Hydroquinones
  • Methoxyphenols
  • Phenethylamines
  • Aromatic compounds
  • Anisoles
  • Halobenzenes
  • Phenyl Esters
  • Amphetamines
Pharmacology
Indication Used to lower high cholesterol levels in the blood.
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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Symptoms of dextrothyroxine overdose are unknown.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
Packagers Not Available
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 235 - 236 oC
Experimental Properties
Property Value Source
logP 4 PhysProp
Predicted Properties
Property Value Source
water solubility 8.98e-03 g/l ALOGPS
logP 1.15 ALOGPS
logP 3.59 ChemAxon Molconvert
logS -4.94 ALOGPS
pKa 7.43 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 92.78 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 126.79 ChemAxon Molconvert
polarizability 49.40 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 853 Link_out
PubChem Substance 46508471 Link_out
ChemSpider 830 Link_out
ChEBI 30659 Link_out
ChEMBL 30659 Link_out
PharmGKB PA449277 Link_out
Drug Product Database 2170299 Link_out
Wikipedia http://en.wikipedia.org/wiki/Dextrothyroxine Link_out
ATC Codes
  • C10AX01
  • H03AA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (60.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Thyroid hormone receptor alpha

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. High affinity receptor for triiodothyronine

Organism class: human
UniProt ID: P10827 Link_out
Gene: THRA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  6. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. Pubmed

2. Thyroid hormone receptor beta-1

Pharmacological action: yes
Actions: agonist

High affinity receptor for triiodothyronine

Organism class: human
UniProt ID: P10828 Link_out
Gene: THRB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. Pubmed
  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
  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. Pubmed
  4. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

3. Thyroid peroxidase

Pharmacological action: unknown

Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4)

Organism class: human
UniProt ID: P07202 Link_out
Gene: TPO Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Visser TJ: The elemental importance of sufficient iodine intake: a trace is not enough. Endocrinology. 2006 May;147(5):2095-7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on December 22, 2010 10:59

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.