T3DB: Tiratricol

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-10-14 21:19:35 UTC

Update Date

2014-12-24 20:27:01 UTC

Accession Number

T3D4983

Identification

Common Name

Tiratricol

Class

Small Molecule

Description

Tiratricol (also known as TRIAC or triiodothyroacetic acid) is a thyroid hormone analogue. It is indicated in the management of thyroid hormone resistance syndrome and is used, in combination with levothyroxine, to suppress thyroid-stimulating hormone production in patients with thyroid cancer. It has been investigated for use in reducing goiter. It has also shown some effectiveness in reducing the atrophy caused when using corticosteroids. Tiratricol has also been widely marketed, under various trade names, as a weight loss aid. In 1999 and 2000, the United States Food and Drug Administration and Health Canada both issued warnings to the public regarding the use of dietary supplements containing tiratricol. Tiratricol is not approved for sale in Canada or the United States. It was once an approved drug in Brazil, but its marketing authorization was suspended in 2003, effectively prohibiting its sale. (Wikipedia)

Compound Type

Industrial/Workplace Toxin
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
3,5,39-triiodothyroacetic acid
Tiracana
TRIAC
Triiodothyroacetic acid
[4-(4-Hydroxy-3-Iodo-Phenoxy)-3,5-Diiodo-Phenyl]-Acetic Acid

Chemical Formula

C₁₄H₉I₃O₄

Average Molecular Mass

621.932 g/mol

Monoisotopic Mass

621.763 g/mol

CAS Registry Number

51-24-1

IUPAC Name

2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]acetic acid

Traditional Name

triac

SMILES

OC(=O)CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1

InChI Identifier

InChI=1S/C14H9I3O4/c15-9-6-8(1-2-12(9)18)21-14-10(16)3-7(4-11(14)17)5-13(19)20/h1-4,6,18H,5H2,(H,19,20)

InChI Key

InChIKey=UOWZUVNAGUAEQC-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Diphenylethers

Direct Parent

Diphenylethers

Alternative Parents

Substituents

Diphenylether
Diaryl ether
Phenoxy compound
2-halophenol
2-iodophenol
Phenol ether
Phenol
1-hydroxy-2-unsubstituted benzenoid
Halobenzene
Iodobenzene
Aryl halide
Aryl iodide
Carboxylic acid derivative
Carboxylic acid
Ether
Monocarboxylic acid or derivatives
Carbonyl group
Organic oxide
Organic oxygen compound
Organooxygen compound
Organoiodide
Organohalogen compound
Hydrocarbon derivative
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Not Available

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Not Available

Appearance

Not Available

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0054 g/L	ALOGPS
logP	5.27	ALOGPS
logP	5.59	ChemAxon
logS	-5.1	ALOGPS
pKa (Strongest Acidic)	2.31	ChemAxon
pKa (Strongest Basic)	-6.4	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	66.76 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	105.67 m³·mol⁻¹	ChemAxon
Polarizability	40.54 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0fk9-0000009000-faf2d387cb07037e1ea8	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0uk9-0000019000-73143b34cfb6772db79c	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00dl-1359220000-af32445877396145eaf4	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00fr-0000049000-9eb0f1e0124f4cae1f4f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00fr-0000279000-8449c1025cf98e1bca75	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-106v-1135912000-88d84a79f0681e18cb48	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral

Mechanism of Toxicity

Tiratricol is a naturally occurring metabolite of T4 (thyroxine) and a structural analog of T3 (triiodothyronine). Low concentrations of tiratricol are found in plasma, but tiratricol has no known role in thyroid physiology. Tiratricol has a high affinity for T3 receptors and suppresses thyroid stimulating hormone (TSH) secretion at therapeutic doses without causing significant peripheral effects, such as increased basal metabolism rate and heart rate. Tiratricol might lower total and LDL cholesterol, and stimulate bone formation. About 67% of an oral dose of tiratricol is absorbed; the half-life is 6 hours. (3) Serum sex hormone-binding globulin levels increased 55 +/- 13% with tiratricol, indicating an augmented hepatic response to tiratricol. Tiratricol had effected the cardiovascular function. Tiratricol has distinct augmented hepatic and skeletal thyromimetic actions of potential therapeutic value. (1)

Metabolism

Tiratricol is a metabolite of T4.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Tiratricol is indicated in the management of thyroid hormone resistance syndrome and is used, in combination with levothyroxine, to suppress thyroid-stimulating hormone production in patients with thyroid cancer. It has been investigated for use in reducing goiter. It has also shown some effectiveness in reducing the atrophy caused when using corticosteroids. Tiratricol has also been widely marketed, under various trade names, as a weight loss aid. In 1999 and 2000, the United States Food and Drug Administration and Health Canada both issued warnings to the public regarding the use of dietary supplements containing tiratricol. (Wikipedia)

Minimum Risk Level

Not Available

Health Effects

Orally, tiratricol can cause severe diarrhea, fatigue, lethargy, and profound weight loss. Heart attacks and strokes are possible, as well as symptoms of hyperthyroidism, including increased appetite, abdominal cramps, tremors, menstrual irregularities, nervousness, insomnia, sweating, intolerance to heat, fever, palpitations, tachycardia, increased pulse and blood pressure, chest pain, and cardiac arrhythmias. Case reports have implicated tiratricol in centrally-mediated hypothyroidism, pseudohypothyroidism, internuclear ophthalmoplegia, and hepatotoxicity. (3) It has been investigated for use in reducing goiter. It has also shown some effectiveness in reducing the atrophy caused when using corticosteroids. (Wikipedia) Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. (2)

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB03604

HMDB ID

Not Available

PubChem Compound ID

5803

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Not Available

General References

Sherman SI, Ringel MD, Smith MJ, Kopelen HA, Zoghbi WA, Ladenson PW: Augmented hepatic and skeletal thyromimetic effects of tiratricol in comparison with levothyroxine. J Clin Endocrinol Metab. 1997 Jul;82(7):2153-8. [9215287 ]
Sherman SI, Ladenson PW: Organ-specific effects of tiratricol: a thyroid hormone analog with hepatic, not pituitary, superagonist effects. J Clin Endocrinol Metab. 1992 Sep;75(3):901-5. [1517383 ]
Natural Medicines - TIRATRICOL [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Thyroid hormone receptor beta

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
Molecular Weight:: 52787.16 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]

Tiratricol (T3D4983)

Structure for T3D4983: Tiratricol

Targets

References