(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid

• ChemBase ID: 334
• Molecular Formular: C15H11I4NO4
• Molecular Mass: 776.87002
• Monoisotopic Mass: 776.68669984
• SMILES: Ic1cc(C[C@H](N)C(=O)O)cc(I)c1Oc1cc(I)c(O)c(I)c1
• Canonical SMILES: OC(=O)[C@H](Cc1cc(I)c(c(c1)I)Oc1cc(I)c(c(c1)I)O)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-/m0/s1
• InChIKey: XUIIKFGFIJCVMT-LBPRGKRZSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
• IUPAC Traditional name: levothyroxine
• Brand Name: Thyreoideum; Thyro-tabs; Thyroxevan; Thyroxin; Thyroxinal; Unithroid; Eltroxin; Euthyrox; Laevoxin; Letter; Levaxin; Levolet; Levothroid; Levothyrox; Levoxine; Levoxyl; Novothyrox; Oroxine; Synthroid; Synthroid Sodium; Thyratabs; Thyrax
• Synonyms: Thyroxine (T4); (-)-Thyroxine; 3,3',5,5'-Tetraiodo-L-thyronine; L-Thryoxin; L-Thyroxine; Laevothyroxinum; Levo-t; Levothyroxine Sodium; Tetraiodothyronine; THX; Thyroxine iodine; Levothyroxin; T4 levothyroxine; O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine; Levothyroxine; L-Thyroxine; O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine; Henning; L-T4; L-Thyroxin; NSC 36397; T4 (hormone); Thyrax; Thyroxinal; ThyroxineAlso see: T425601; T4; 3,3′,5,5″-Tetraiodo-L-thyronine; L-Thyroxine; Levothyroxine; Thyreoideum; Thyroxin; Thyroxine; 3-[4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine; L-甲状腺素; 甲状腺素 (T4); 3,3′,5,5″-四碘代-L-甲状腺原氨酸; 3-[4-(4-羟基-3,5-二碘苯氧基)-3,5-二碘苯基]-L-丙氨酸; L-甲状腺素

Database IDs

• CAS Number: 51-48-9
• EC Number: 200-101-1
• MDL Number: MFCD00002595
• Beilstein Number: 2228515
• PubChem SID: 46507672; 24900033; 24899990; 160963797
• PubChem CID: 5819

CALCULATED PROPERTIES

JChem

• Acid pKa: 0.27336746
• H Acceptors: 4
• H Donor: 3
• LogD (pH = 5.5): 3.722463
• LogD (pH = 7.4): 3.4409168
• Log P: 3.727307
• Molar Refractivity: 126.788 cm^3
• Polarizability: 50.46104 Å^3
• Polar Surface Area: 92.78 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 1.15
• LOG S: -4.94
• Solubility (Water): 8.98e-03 g/l

PROPERTIES

Physical Property

• Solubility: 0.105 mg/mL; Methanol
• Apperance: powder; Tan Solid
• Melting Point: ~235 °C (dec.); >300°C (dec.); 223 °C (dec.)(lit.); 235-236°C (decomposes)
• Optical Rotation: [α]20/D -5.3±0.5°, c = 1% in ethanol/1 M NaOH (2:1)
• Hydrophobicity(logP): 4

Safety Information

• Storage Condition: 0°C; -20°C; -20°C Freezer, Under Inert Atmosphere
• RTECS: YP2833500
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C; -70°C

Pharmacology Properties

• Gene Information: human ... TTR(7276); human ... TTR(7276)mouse ... Cnr2(12802)rat ... Cnr1(25248)

Product Information

• Purity: ≥97.0% (sum of enantiomers, HPLC); ≥98% (HPLC)
• Grade: BCR® certified Reference Material
• Salt Data: Free Base
• Potency: 5-50 ng/mL
• Suitability: suitable for cell culture
• Product Line: BioReagent
• Linear Formula: HOC6H2(I)2OC6H2(I)2CH2CH(NH2)CO2H

DETAILS

MP Biomedicals - 02152145

Free Acid
Crystalline

DrugBank - DB00451

• Drug 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]
• Indication: For use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.
• Pharmacology: Levothyroxine (T₄) is a synthetically prepared levo isomer of thyroxine, the major hormone secreted from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine (T₃) which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold.
• Toxicity: LD₅₀=20 mg/kg (orally in rat). 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
• Biotransformation: Approximately 70% of secreted T₄ is deiodinated to equal amounts of T₃ and reverse triiodothyronine (rT₃), which is calorigenically inactive. Elimination of T₄ and T₃ involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T₄ metabolites have been identified.
• Absorption: Bioavailability varies from 48% to 80%. Human studies have confirmed the importance of an intact jejunum and ileum for levothyroxine absorption and have shown some absorption from the duodenum.
• Half Life: T₄, 6 to 7 days. T₃, 1 to 2 days.
• Protein Binding: > 99% to serum proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA)
• Elimination: Thyroid hormones are primarily eliminated by the kidneys.
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S2599

Research Area: Endocrinology
Biological Activity:
L-Thyroxine is a synthetic form of thyroxine and a hormone replacement drug. L-Thyroxine is typically used to treat hypothyroidism. L-Thyroxine may also be used to treat goiter via its ability to lower thyroid-stimulating hormone (TSH), a hormone that is considered goiter-inducing.

Sigma Aldrich - T2376

Biochem/physiol Actions
L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis.
Packaging
1, 5 g in glass bottle
100, 500 mg in glass bottle
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. T2376.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Sigma Aldrich - T1775

Biochem/physiol Actions
L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis.
Reconstitution
To prepare 20 μg/ml stock solution, dissolve in 50 ml sterile culture medium per mg thyroxine.
Physical form
powder-0 °C; stock-frozen in working aliquots, avoid repeated freeze/thaw, solution stable 2-8 °C, 30 days

Sigma Aldrich - IRMM468

Biochem/physiol Actions
L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis.
Legal Information
BCR is a registered trademark of European Commission

Sigma Aldrich - 89405

Biochem/physiol Actions
L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis.
Other Notes
Review1

Toronto Research Chemicals - T425600

One of the thyroid hormones involved in the maintenance of metabolic homeostasis. Synthesized and stored as amino acid residues of thyroglobulin, the major protein component of the thyroid follicular colloid. Synthesis and secretion are regulated by the p

REFERENCES

• Post, A., et al.: Anal. Profiles Drug Subs., 5, 225 (1976)
• Nelson, J.C., et al.: Clin. Chem., 34, 1737 (1976)
• Fischer, D.A., et al.: Clin. Chem., 42, 135 (1976)
• Cavalieri, R.R., et al.: Thyroid, 7, 177 (1976)