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Record Information
Version2.0
Created at2005-11-16 15:48:42 UTC
Updated at2021-07-01 14:27:35 UTC
NP-MRD IDNP0000418
Secondary Accession NumbersNone
Natural Product Identification
Common NameThyroxine
DescriptionThyroxine (3,5,3′,5′-tetraiodothyronine) or T4 is one of two major hormones derived from the thyroid gland, the other being triiodothyronine (T3). The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. In humans, the ratio of T4 to T3 released into the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by enzymes known as deiodinases (5′-iodinase). Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Iodine is critical to the synthesis of thyroxine and other thyroid hormones. Through a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues found in the thyroglobulin protein, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one molecule of MIT and one molecule of DIT produces triiodothyronine. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Iodide is actively absorbed from the bloodstream and concentrated in the thyroid follicles where thyroxine is produced. If there is a deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in a condition called goitre. More specifically, the lack of thyroid hormones will lead to decreased negative feedback on the pituitary gland, leading to increased production of thyroid-stimulating hormone, which causes the thyroid to enlarge, leading to goitre. Thyroxine can be peripherally de-iodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. They act on nearly every cell in the body. In particular, thyroid hormones act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis. Levothyroxine, a manufactured form of thyroxine, was the most prescribed medication in the United States with more than 114 million prescriptions.
Structure
Thumb
Synonyms
ValueSource
3,3',5,5'-Tetraiodo-L-thyronineChEBI
3,5,3',5'-TETRAIODO-L-thyronineChEBI
4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodo-L-phenylalanineChEBI
L-T4ChEBI
LevothyroxinChEBI
LevothyroxineChEBI
LT4ChEBI
O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosineChEBI
T4ChEBI
L-ThyroxineKegg
O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosineKegg
3,5,3'5'-Tetraiodo-L-thyronineKegg
ForthyronKegg
(-)-ThyroxineHMDB
3,3',5,5''-Tetraiodo-L-thyronineHMDB
3,5,3',5'-TetraiodothyronineHMDB
D-ThyroxineHMDB
DL-ThyroxinHMDB
HenningHMDB
L-3,5,3',5'-TetraiodothyronineHMDB
L-ThyroxinHMDB
LaevothyroxinumHMDB
LevothroidHMDB
Levothyroxine sodiumHMDB
LevothyroxinumHMDB
LevoxylHMDB
Prestwick_548HMDB
SynthroidHMDB
TetraiodothyronineHMDB
TetrametHMDB
THXHMDB
ThyratabsHMDB
ThyraxHMDB
ThyreoideumHMDB
ThyroxinHMDB
ThyroxinalHMDB
Thyroxine I 125HMDB
Thyroxine iodineHMDB
Allphar brand OF levothyroxine sodiumHMDB
BerlthyroxHMDB
Delalande, levothyroxinHMDB
DexnonHMDB
EferoxHMDB
EltroxinHMDB
Kern brand OF levothyroxine sodiumHMDB
L-ThyroxHMDB
L-Thyroxin henningHMDB
L-Thyroxin betaHMDB
L-Thyroxine rocheHMDB
Levothyroxin deladandeHMDB
LévothyroxHMDB
Merck lipha santé brand OF levothyroxine sodiumHMDB
Nourypharma brand OF levothyroxine sodiumHMDB
OroxineHMDB
Aventis brand OF levothyroxine sodiumHMDB
EuthyroxHMDB
EutiroxHMDB
Forest brand OF levothyroxine sodiumHMDB
Genpharm brand OF levothyroxine sodiumHMDB
GlaxoSmithKline brand OF levothyroxine sodiumHMDB
Goldshield brand OF levothyroxine sodiumHMDB
LThyroxin henningHMDB
Levo-THMDB
Sanofi synthelabo brand OF levothyroxine sodiumHMDB
Sigma brand OF levothyroxine sodiumHMDB
SynthroxHMDB
ThevierHMDB
Watson brand OF levothyroxine sodiumHMDB
Berlin chemie brand OF levothyroxine sodiumHMDB
Delalande brand OF levothyroxine sodiumHMDB
EltroxineHMDB
Hexal brand 2 OF levothyroxine sodiumHMDB
L Thyroxine rocheHMDB
NovothyralHMDB
TiroidineHMDB
Vortex brand OF levothyroxine sodiumHMDB
Abbot brand OF levothyroxine sodiumHMDB
Berlin-chemie brand OF levothyroxine sodiumHMDB
Byk brand OF levothyroxine sodiumHMDB
Deladande, levothyroxinHMDB
GlaxoWellcome brand OF levothyroxine sodiumHMDB
Henning berlin brand OF levothyroxine sodiumHMDB
Hexal brand 1 OF levothyroxine sodiumHMDB
L ThyroxHMDB
L Thyroxin henningHMDB
L Thyroxin betaHMDB
L ThyroxineHMDB
LThyroxin betaHMDB
Leo, tiroxinaHMDB
Levo THMDB
LevoTHMDB
LevothyroidHMDB
Levothyroxin delalandeHMDB
LevoxineHMDB
Merck brand OF levothyroxine sodiumHMDB
Monarch brand OF levothyroxine sodiumHMDB
Mova brand OF levothyroxine sodiumHMDB
NovothyroxHMDB
O-(4-Hydroxy-3,5-diiodophenyl) 3,5-diiodo-L-tyrosineHMDB
O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodotyrosineHMDB
Roche brand OF levothyroxine sodiumHMDB
Rudefsa brand OF levothyroxine sodiumHMDB
Sodium levothyroxineHMDB
T4 Thyroid hormoneHMDB
Thyroid hormone, T4HMDB
Tiroxina leoHMDB
UnithroidHMDB
Betapharm brand OF levothyroxine sodiumHMDB
Chemical FormulaC15H11I4NO4
Average Mass776.8700 Da
Monoisotopic Mass776.68668 Da
IUPAC Name(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Traditional Namelevothyroxine
CAS Registry Number51-48-9
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
InChI Identifier
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-/m0/s1
InChI KeyXUIIKFGFIJCVMT-LBPRGKRZSA-N
Experimental Spectra
Spectrum TypeDescriptionDepositor EmailDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, 100%_DMSO, experimental)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, 100%_DMSO, experimental)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Predicted Spectra
Not Available
Chemical Shift Submissions
Not Available
Species
Species of Origin
Species NameSourceReference
Homo sapiensLOTUS Database
Mus musculusLOTUS Database
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenylalanine and derivatives. Phenylalanine and derivatives 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPhenylalanine and derivatives
Alternative Parents
Substituents
  • Phenylalanine or derivatives
  • Diphenylether
  • Diaryl ether
  • 3-phenylpropanoic-acid
  • Alpha-amino acid
  • Amphetamine or derivatives
  • L-alpha-amino acid
  • Phenoxy compound
  • Phenol ether
  • 2-halophenol
  • 2-iodophenol
  • Aralkylamine
  • Phenol
  • Halobenzene
  • Iodobenzene
  • Aryl halide
  • Aryl iodide
  • Benzenoid
  • Monocyclic benzene moiety
  • Amino acid
  • Carboxylic acid
  • Ether
  • Monocarboxylic acid or derivatives
  • Organoiodide
  • Organonitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxide
  • Carbonyl group
  • Primary amine
  • Amine
  • Hydrocarbon derivative
  • Primary aliphatic amine
  • Organic oxygen compound
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point235.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.009 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity126.79 m³·mol⁻¹ChemAxon
Polarizability49.4 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
HMDB IDHMDB0000248
DrugBank IDDB00451
Phenol Explorer Compound IDNot Available
FoodDB IDFDB112159
KNApSAcK IDNot Available
Chemspider ID5614
KEGG Compound IDC01829
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevothyroxine
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID18332
Good Scents IDNot Available
References
General References
  1. Gil'miiarova FN, Pervova IuV, Radomskaia VM, Gergel' NI, Tarasova SV: [Levels of unified metabolites and thyroid hormones in blood and oral fluid of children with minimal brain dysfunction]. Biomed Khim. 2004 Mar-Apr;50(2):204-10. [PubMed:15179829 ]
  2. Kahan IL, Varsanyi-Nagy M, Toth M, Nadrai A: The possible role of tear fluid thyroxine in keratoconus development. Exp Eye Res. 1990 Apr;50(4):339-43. [PubMed:2338121 ]
  3. Jagannathan NR, Tandon N, Raghunathan P, Kochupillai N: Reversal of abnormalities of myelination by thyroxine therapy in congenital hypothyroidism: localized in vivo proton magnetic resonance spectroscopy (MRS) study. Brain Res Dev Brain Res. 1998 Aug 8;109(2):179-86. [PubMed:9729372 ]
  4. Kurz W, Wittlinger G, Litmanovitch YI, Romanoff H, Pfeifer Y, Tal E, Sulman FG: Effect of manual lymph drainage massage on urinary excretion of neurohormones and minerals in chronic lymphedema. Angiology. 1978 Oct;29(10):764-72. [PubMed:717839 ]
  5. Randolph VS: Four clinical chemistry analyses for pediatric patients: glycosylated hemoglobin, free bilirubin, sweat electrolytes, neonatal thyroxine. Am J Med Technol. 1982 Jan;48(1):15-22. [PubMed:7041647 ]
  6. van Wassenaer AG, Stulp MR, Valianpour F, Tamminga P, Ris Stalpers C, de Randamie JS, van Beusekom C, de Vijlder JJ: The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant. Clin Endocrinol (Oxf). 2002 May;56(5):621-7. [PubMed:12030913 ]
  7. Etling N, Gehin-Fouque F, Vielh JP, Gautray JP: The iodine content of amniotic fluid and placental transfer of iodinated drugs. Obstet Gynecol. 1979 Mar;53(3):376-80. [PubMed:424113 ]
  8. Zenovko EI, Pavlov BA, Koreshkov GG, Gudukina GN, Sonkina EG: [Hypothalamo-pituitary-thyroid system in patients with rheumatoid arthritis]. Ter Arkh. 1998;70(1):49-52. [PubMed:9532653 ]
  9. Hays MT, McGuire RA, Hoogeveen JT, Diezeraad KN: Measurement method for radioactive thyroxine, triiodothyronine, iodide, and iodoprotein in samples with low activity. J Nucl Med. 1980 Mar;21(3):225-32. [PubMed:7365515 ]
  10. Benvenga S, Alesci S, Trimarchi F: High-density lipoprotein-facilitated entry of thyroid hormones into cells: a mechanism different from the low-density lipoprotein-facilitated entry. Thyroid. 2002 Jul;12(7):547-56. [PubMed:12193297 ]
  11. Hausman GJ, Wright JT, Latimer A, Watson R, Martin RJ: The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus. Obes Res. 1993 Sep;1(5):345-56. [PubMed:16350585 ]
  12. Gil-Loyzaga P, Remezal M, Mollicone R, Ibanez A, Oriol R: H and B human blood-group antigen expression in cochlear hair cells is modulated by thyroxine. Cell Tissue Res. 1994 May;276(2):239-43. [PubMed:8020061 ]
  13. Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, Galan JM, Barrios V, Sancho J: Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005 Mar 15;142(6):412-24. [PubMed:15767619 ]
  14. Bode HH, Vanjonack WJ, Crawford JD: Mitigation of cretinism by breast-feeding. Pediatrics. 1978 Jul;62(1):13-6. [PubMed:683777 ]
  15. Marks P, Anderson J, Vincent R: Aldosterone in myxoedema. Lancet. 1978 Dec 16;2(8103):1277-8. [PubMed:82781 ]
  16. Sutherland RL, Simpson-Morgan MW: The thyroxine-binding properties of serum proteins. A competitive binding technique employing sephadex G-25. J Endocrinol. 1975 Jun;65(3):319-32. [PubMed:807668 ]
  17. Braley-Mullen H, Sharp GC: A thyroxine-containing thyroglobulin peptide induces both lymphocytic and granulomatous forms of experimental autoimmune thyroiditis. J Autoimmun. 1997 Dec;10(6):531-40. [PubMed:9451592 ]
  18. Raghu P, Reddy GB, Sivakumar B: Inhibition of transthyretin amyloid fibril formation by 2,4-dinitrophenol through tetramer stabilization. Arch Biochem Biophys. 2002 Apr 1;400(1):43-7. [PubMed:11913969 ]
  19. Hekimsoy Z, Oktem IK: Serum creatine kinase levels in overt and subclinical hypothyroidism. Endocr Res. 2005;31(3):171-5. [PubMed:16392619 ]