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Liothyronine

PubChem CID
5920
Structure
Liothyronine_small.png
Liothyronine_3D_Structure.png
Molecular Formula
Synonyms
  • liothyronine
  • triiodothyronine
  • 3,3',5-Triiodo-L-thyronine
  • 6893-02-3
  • Liothyronin
Molecular Weight
650.97 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
3,3',5-triiodo-L-thyronine is an iodothyronine compound having iodo substituents at the 3-, 3'- and 5-positions. Although some is produced in the thyroid, most of the 3,3',5-triiodo-L-thyronine in the body is generated by mono-deiodination of L-thyroxine in the peripheral tissues. Its metabolic activity is about 3 to 5 times that of L-thyroxine. The sodium salt is used in the treatment of hypothyroidism. It has a role as a thyroid hormone, a human metabolite and a mouse metabolite. It is an iodophenol, a 2-halophenol and an iodothyronine. It is a conjugate acid of a 3,3',5-triiodo-L-thyroninate. It is a tautomer of a 3,3',5-triiodo-L-thyronine zwitterion.
Liothyronine is a thyroidal hormone T3 which is normally produced by the thyroid gland in a ratio 4:1 when compared with T4: T3. Liothyronine is the active form of thyroxine which is composed in a basic chemical structure by a tyrosine with bound iodine. The exogenous liothyronine product was developed by King Pharmaceuticals and FDA approved in 1956.
Liothyronine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
See also: Liothyronine Sodium (has salt form); Liotrix (is active moiety of); Levothyroxine; Liothyronine (component of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Liothyronine.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C15H12I3NO4/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22/h1-4,6,12,20H,5,19H2,(H,21,22)/t12-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

AUYYCJSJGJYCDS-LBPRGKRZSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C1=CC(=C(C=C1OC2=C(C=C(C=C2I)C[C@@H](C(=O)O)N)I)I)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C15H12I3NO4
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

6893-02-3

2.3.2 Deprecated CAS

57164-27-9, 7013-53-8

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 PharmGKB ID

2.3.15 Pharos Ligand ID

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 3,3',5-Triiodothyronine
  • Cytomel
  • Liothyronine
  • Liothyronine Sodium
  • T3 Thyroid Hormone
  • Thyroid Hormone, T3
  • Triiodothyronine

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
650.97 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
1.7
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
650.7901 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
650.7901 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
92.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
23
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
402
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Color / Form

CRYSTALS
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

3.2.3 Boiling Point

563 ºC at 760 mmHg
'MSDS'

3.2.4 Melting Point

230 ºC
'MSDS'

3.2.5 Solubility

11.4 [ug/mL] (The mean of the results at pH 7.4)
Very slightly soluble
'MSDS'
In water, 3.958 mg/l at 37 °C.
Yalkowsky SH, Dannenfelser RM; Aquasol Database of Aqueous Solubility. Version 5. College of Pharmacy, Univ of Ariz - Tucson, AZ. PC Version (1992)
Soluble in dilute alkalies with the formation of a brownish, water-soluble, sodium salt. Insoluble in propylene glycol.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

3.2.6 LogP

3
'MSDS'
log Kow = 0.93
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 129

3.2.7 LogS

-5.22
ADME Research, USCD

3.2.8 Optical Rotation

Optical rotation = +21.5 deg at 29.5 °C/D (c = 4.75 in a mixture of 1 part N hydrogen chloride + 2 parts ethanol).
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

3.2.9 Decomposition

When heated to decomposition it emits toxic fumes of nitroxides, /hydrogen iodide/.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2054

3.2.10 Dissociation Constants

pKa
8.4
Harrold M. and Zavod R. 2013. Medicinal Chemistry.

3.2.11 Collision Cross Section

204.77 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

191.01 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111
205.3 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

209.7 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

185.23 Ų [M+Na-2H]- [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

209.1 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

194.3 Ų [M+Na]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

209.3 Ų [M+H]+

194.5 Ų [M+Na]+

S50 | CCSCOMPEND | The Unified Collision Cross Section (CCS) Compendium | DOI:10.5281/zenodo.2658162

3.2.12 Other Experimental Properties

DECOMPOSES @ 236-237 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941
DECOMPOSES @ 202-203 °C /HYDROCHLORIDE/
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941
LIGHT-TAN, CRYSTALLINE POWDER /LIOTHYRONINE SODIUM USP/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 909
SPECIFIC OPTICAL ROTATION: +21.5 DEG @ 29.5 °C/D (C= 4.75 IN MIXT OF 1 PART N HYDROGEN CHLORIDE + 2 PARTS ETHANOL) /HYDROCHLORIDE/
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Thyroid Hormones

3.3.2 Endocrine Disruptors

Potential endocrine disrupting compound
S109 | PARCEDC | List of 7074 potential endocrine disrupting compounds (EDCs) by PARC T4.2 | DOI:10.5281/zenodo.10944198

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
100%_DMSO
pH
7.00
Shifts [ppm]:Intensity
6.86:28.70, 3.10:7.71, 2.85:8.04, 6.64:11.01, 7.03:17.59, 3.13:7.07, 2.84:7.23, 2.87:7.72, 6.63:10.43, 7.82:100.00, 7.03:17.19, 6.87:23.85, 3.11:8.69, 3.49:11.35, 3.49:10.96, 3.48:10.85, 2.83:6.44, 3.50:9.66, 6.62:10.33, 3.13:7.38, 6.64:11.31
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
271772
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
271772
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 2D NMR Spectra

4.2.1 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
100%_DMSO
pH
7.00
Shifts [ppm] (F2:F1):Intensity
6.63:116.20:0.54, 3.49:54.78:0.76, 7.82:140.76:0.52, 2.85:34.85:0.32, 3.12:34.85:0.21, 6.86:114.86:0.54, 7.03:124.33:1.00
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4.3 Mass Spectrometry

4.3.1 MS-MS

1 of 8
View All
Spectra ID
Instrument Type
LC-ESI-QQ (API3000, Applied Biosystems)
Ionization Mode
Negative
Top 5 Peaks
650.0 1
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2 of 8
View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

126.905 100

72.0092 4.01

448.8542 2.17

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4.3.2 LC-MS

1 of 25
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.211 min
Precursor m/z
651.7973
Precursor Adduct
[M+H]+
Top 5 Peaks

605.7912 999

507.8656 185

478.8873 112

606.7929 86

651.7996 42

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License
CC BY
2 of 25
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.212 min
Precursor m/z
651.7973
Precursor Adduct
[M+H]+
Top 5 Peaks

605.7907 999

651.7954 546

507.8644 134

606.7917 74

634.7694 61

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License
CC BY

4.3.3 Other MS

MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
651.797
Instrument
Orbitrap
Ionization Mode
positive
Top 5 Peaks

225.078888 100

198.067276 73.04

605.788269 67.68

478.888397 45.26

507.863983 39.80

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4.4 IR Spectra

4.4.1 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Calbiochem, EMD Chemicals, Inc., an Affiliate of Merck KGaA, Darmstadt, Germany
Catalog Number
64245
Lot Number
601689
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Frey Scientific Company
Catalog Number
79630
Lot Number
AD-5508
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Frey Scientific Company
Catalog Number
79630
Lot Number
AD-5508
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Other Spectra

LONG, BIREFRINGENT NEEDLES /HYDROCHLORIDE/
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Liothyronine is officially approved for the following indications: - Replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism. - As an adjunct therapy to surgery and radioiodine in the management of thyroid cancer. - As a diagnostic agent in suppression tests for mild hyperthyroidism or thyroid gland autonomy. In general terms, exogenous liothyronine is used to replace insufficient hormonal production and restore T3 plasma levels. The lack of liothyronine can be presented as a pale and puffy face, coarse, brittle hair, dry skin, croaky voice and constipation as well as irregular periods, drowsiness, and lethargy. Liothyronine should never be used in the suppression of benign nodules and nontoxic diffuse goiter in iodine-sufficient patients nor in the treatment of hyperthyroidism during the recovery phase of subacute thyroiditis.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Thyroid Hormones

7.3 FDA National Drug Code Directory

7.4 Drug Labels

Active ingredient and drug

7.5 Clinical Trials

7.5.1 ClinicalTrials.gov

7.5.2 EU Clinical Trials Register

7.6 Therapeutic Uses

LIOTHYRONINE SODIUM...MAY BE USEFUL...WHEN HYPOTHYROIDISM HAS RECENTLY SUPERVENED FROM OVERTREATMENT WITH ANTITHYROID DRUG OR FOLLOWING TREATMENT WITH RADIOIODINE OR THYROIDECTOMY, & IN RARE EVENT OF COMA DUE TO MYXEDEMA. /LIOTHYRONINE SODIUM/
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1408
WITH THIS DOSE /EXPERIMENTAL DOSE OF 1 MG SC ADMIN/, A METABOLIC RATE OF MINUS 40% CAN BE RAISED TO NORMAL WITHIN 24 HR. MAXIMAL RESPONSE OCCURS IN 2 DAYS OR LESS.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1408
Triiodothyronine (liothyronine sodium) may be used occasionally when a quicker onset of action is desired as, for example, in the rare presentation of myexedema coma or for preparing a patient for (131)I therapy for treatment of thyroid cancer.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1395
MEDICATION (VET):: USED FOR...OBESITY, BILATERAL ALOPECIA, ACANTHOSIS, DRY SKIN, WRINKLED SKIN, POOR HAIR COLOR, STRAIGHTNESS IN CURLY HAIR COATS, LACK OF "WIRE" IN WIRE-HAIRED BREEDS, LETHARGY, SLOW GROWTH, UNTHRIFTINESS, LIBIDO LOSS, POOR BREEDING EFFICIENCY, URINARY INCONTINENCE, & LACK OF MENTAL & PHYSICAL VIGOR ESP IN OLDER ANIMALS.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 312
For more Therapeutic Uses (Complete) data for LIOTHYRONINE (12 total), please visit the HSDB record page.

7.7 Drug Warnings

VET: AVOID EXCESSIVE DOSAGE IN CASES WITH WEAK HEARTS.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 312
LIOTHYRONINE LABELED WITH EITHER (125)I OR (131)I...FOR IN VITRO EVALUATION OF THYROID FUNCTION. DUE TO HIGH SPECIFIC ACTIVITY REQUIRED, RADIATION DAMAGE CAN EASILY OCCUR. ... DOSE IS NOT FOR INTERNAL USE.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 513
IN ABSENCE OF HYPERTHYROIDISM, THYROID HORMONES DO NOT IMPROVE SKIN CONDITIONS, MENTAL DEPRESSION, FATIGUE, LETHARGY, IRRITABILITY, NERVOUSNESS, MENSTRUAL IRREGULARITIES, & OTHER ENDOCRINE & REPRODUCTIVE DISORDERS, & THERE IS DANGER THAT UNTOWARD EFFECTS MAY BE PRODUCED.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 910
...THYROID HORMONES /EG, LIOTHYRONINE/ OR MIXTURES CONTAINING THEM SHOULD NOT BE USED WITHOUT SPECIFIC INDICATION OF DEFICIENCY. ...TO EFFECT WEIGHT LOSS IN EUTHYROID OBESE INDIVIDUALS...THYROID HORMONES OR PREPN CONTAINING THEM SHOULD NOT BE USED FOR THIS PURPOSE.
American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 602
For more Drug Warnings (Complete) data for LIOTHYRONINE (17 total), please visit the HSDB record page.

7.8 Reported Fatal Dose

PROBABLE ORAL LETHAL DOSE (HUMAN) 0.5-5 G/KG, BETWEEN 1 OZ & 1 PINT (OR 1 LB) FOR 70 KG PERSON (150 LB). /THYROID/
Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-52

7.9 Biomarker Information

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

In hormonal replacement, liothyronine is more potent and present a faster action when compared to levothyroxine but the time of action is significantly shorter. The type of treatment needs to be well evaluated as the fast correction of thyroid hormones in certain diseases presents additional risks such as heart failure. The onset of activity is observed a few hours after administration and the maximum effect is observed after 2-3 days. Treatment with liothyronine has been shown to produce normal plasma levels of T3 hormone but to have no effect on the T4 plasma concentration.

8.2 FDA Pharmacological Classification

FDA UNII
06LU7C9H1V
Active Moiety
LIOTHYRONINE
Pharmacological Classes
Established Pharmacologic Class [EPC] - l-Triiodothyronine
Pharmacological Classes
Chemical Structure [CS] - Triiodothyronine
FDA Pharmacology Summary
Liothyronine is a l-Triiodothyronine.

8.3 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

8.4 Bionecessity

STATE OF DEFICIENCY: WHEN THERE IS A DEFICIENCY OF IODINE IN RAT THYROID... THE RATIO OF THYROXINE TO TRIIODOTHYRONINE DECREASES FROM 4:1 TO 1:3.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1401
STATE OF DEFICIENCY: IN ABSENCE OF...TRIIODOTHYRONINE, GROWTH IS DEFICIENT, PARTICULARLY AT YOUNGER AGES.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1406

8.5 Absorption, Distribution and Excretion

Absorption
Thyroid hormones are well absorbed orally. From these hormones, liothyronine is almost completely absorbed and it does not present changes in the absorption rate due to concomitant administration of food.liothyronin Multiple administration of 50 mcg of liothyronine provided a maximal plasma concentration of total T3 of 346 ng/dL in about 2.5 hours with an AUC of 4740 ng.h/dL.
Route of Elimination
The main elimination of thyroid hormones is known to be done via the kidneys from which less than 2.5% of the excreted drug is represented by the unchanged drug. This elimination route is reduced with age. A portion of the metabolic products of liothyronine is excreted to the bile and gut where they can be part of enterohepatic recirculation.
Volume of Distribution
The reported volume of distribution of liothyronine is reported to be of 0.1-0.2 L/kg.
Clearance
There are no reports obtaining this value specifically.
WHILE TRIIODOTHYRONINE IS MUCH LESS FIRMLY BOUND /TO PROTEIN THAN IS THYROXINE/, THE QUANTITY THAT IS FREE IS STILL SMALL PERCENTAGE OF TOTAL.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1402
THE DAILY SECRETION OF /TRIIODOTHYRONINE/ IN NORMAL MAN IS APPROXIMATELY...25 UG.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1402
LIOTHYRONINE IS ERRATICALLY ABSORBED FROM GI TRACT, & 30 TO 40% MAY BE RECOVERED FROM STOOLS.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 909
INTESTINAL ABSORPTION OF THYROID HORMONES WERE MARKEDLY DIMINISHED AFTER INTESTINAL BYPASS SURGERY & RESTORED TO NORMAL AFTER REVERSAL OF SHUNT.
AZIZI F ET AL; ANN INTERN MED 90 (JUN): 941-2 (1979)
Liothyronine sodium is almost completely absorbed from the GI tract (about 95%) following oral administration. /Liothyronine sodium/
McEvoy, G.K. (ed.). American Hospital Formulary Service-Drug Information 19 98. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1998 (Plus Supplements)., p. 2646

8.6 Metabolism / Metabolites

Liothyronine is mainly metabolized in the liver where it is deiodinated to diiodothyronine and monoiodothyronine followed by conjugation with glucuronides and sulfates. One of the formed metabolites formed by the conjugation and decarboxylation is tiratricol. The iodine released by the metabolism of liothyronine is later taken and used within the thyroid cells.
THE LIVER CONJUGATES THYROXINE & TRIIODOTHYRONINE WITH GLUCURONIC & SULFURIC ACIDS THROUGH THE PHENOLIC HYDROXYL GROUP, & EXCRETES THESE CONJUGATES & SMALL AMT OF FREE COMPOUNDS IN THE BILE.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1403
Triiodothyronine has known human metabolites that include (2S,3S,4S,5R)-6-[4-[4-[(2S)-2-amino-2-carboxyethyl]-2,6-diiodophenoxy]-2-iodophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560
Half Life: 2.5 days

8.7 Biological Half-Life

The half-life of liothyronine is reported to be between 1 and 2 days.

8.8 Mechanism of Action

Liothyronine replaces endogenous thyroid hormone and then exerts its physiologic effects by controlling DNA transcription and protein synthesis. This effect on DNA is obtained by the binding of liothyronine to the thyroid receptors attached to DNA. Exogenous liothyronine exerts all the normal effects of the endogenous thyroid T3 hormone. Hence, it increases energy expenditure, accelerates the rate of cellular oxidation stimulating growth, maturation, and metabolism of the body tissues, aids in myelination of nerves and development of synaptic processes in the nervous system and enhances carbohydrate and protein metabolism.
LIOTHYRONINE IS ONLY LOOSELY BOUND TO PLASMA PROTEINS & HENCE DOES NOT ELEVATE PLASMA BOUND IODINE SIGNIFICANTLY...PBI MAY ACTUALLY BE LOWERED, BECAUSE OF HOMEOSTATIC DECR IN THYROXINE RELEASE FROM THYROID GLAND.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 909
TRIIODOTHYRONINE INCR METABOLIC RATE & OXYGEN CONSUMPTION OF ANIMAL TISSUES.
Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 885

8.9 Human Metabolite Information

8.9.1 Tissue Locations

  • Adipose Tissue
  • Adrenal Gland
  • Epidermis
  • Fibroblasts
  • Intestine
  • Neuron
  • Placenta
  • Platelet
  • Skeletal Muscle
  • Testis
  • Thyroid Gland

8.9.2 Cellular Locations

  • Cytoplasm
  • Extracellular
  • Membrane

8.9.3 Metabolite Pathways

8.10 Biochemical Reactions

8.11 Transformations

9 Use and Manufacturing

9.1 Uses

THERAP CAT: Thyroid hormone; THERAP CAT (VET): Thyroid hormone.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941
Used as replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyrodism during the recovery phase of subacute thyroiditis.

9.2 Methods of Manufacturing

Formation from diiodothyronine: Roche et al., Biochem Biophys Acta 11, 215 (1953). Isoln from thyroid gland and synthesis: Gross, Pitt-Rivers, Biochem J 53, 645 (1953); Roche et al., Bull Soc Chim France 4, 462 (1957); Plati, Wenner, U.S. pat 2,784,222 (1957 to Hoffmann-La Roche); Pitt-Rivers, Gross, U.S. pat 2,823,164 (1958 to Nat Res Dev Corp); Razdan, Wetherill, U.S. pat 2,993,928 (1961 to Glaxo).
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

9.3 Formulations / Preparations

LIOTHYRONINE SODIUM, USP (CYTOMEL), IS...DESIGNATION FOR SALT OF L-TRIIODOTHYRONINE. ...ALSO IS MARKETED AS TABLETS CONTAINING 5, 25, & 50 UG. KITS FOR PREPN OF POWDER FOR INJECTION ARE AVAILABLE FROM MFR. /LIOTHYRONINE SODIUM/
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1408
ORAL TABLETS 5, 25, & 50 MCG; INJECTION: POWDER (FOR SOLN) 114 UG/ML. NOT COMMERCIALLY AVAILABLE; MFR WILL SUPPLY KIT UPON REQUEST.,.
American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 606
/SODIUM SALT LIOTHYRONINE IS/ COMMONLY USED FORM. /LIOTHYRONINE SODIUM/.
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 1244
...TRIIODOTHYRONINE REPRESENTS RELATIVELY MINOR FRACTION (ABOUT 5%) /OF ORGANIC IODINE/.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1402

9.4 General Manufacturing Information

IN DOGS & MAN IT HAS APPROX 2,500 TIMES THE ORAL POTENCY OF OFFICIAL THYROID PREPN.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 312
Possesses 5 times the activity of L-thyroxine.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 941

10 Identification

10.1 Analytic Laboratory Methods

USE OF 8-ANILINO-1-NAPHTHALENESULFONIC ACID IN RADIOIMMUNOASSAY OF TRIIODOTHYRONINE.
BROWN ML; J PHARM SCI 63 (AUG): 1214-7 (1974)
EVALUATION OF RAPID & SIMPLE TECHNIQUE FOR RADIOIMMUNOASSAY OF TRIIODOTHYRONINE (T3). METHOD CAN BE USED TO AID DIAGNOSIS & MANAGEMENT OF PATIENTS WITH THYROID DISORDERS.
BURMAN K ET AL; J NUCL MED 16 (JUL): 662-5 (1975)
THYROXINE (T4) IS DETECTED BY THIN LAYER CHROMATOGRAPHY. IODO THYRONINE CONTENT OF LIOTHYRONINE SODIUM IS EST BY LIQUID CHROMATOGRAPHY.
CIERI UR, ILLUMINATI JC; J ASSOC OFF ANAL CHEM 60 (MAY): 628-34 (1977)
ANALYSIS OF SODIUM LEVOTHYROXINE OR SODIUM LIOTHYRONINE IN TABLETS. ACTIVE INGREDIENTS WERE ISOLATED & ANALYZED SPECTROPHOTOMETRICALLY FOLLOWING REDN TO TRIIODIDE ION. METHOD MAY BE APPLIED TO DOSAGE LEVELS AS LOW AS 5 UG.
GRAHAM ET AL; J PHARM SCI 63 (MAY): 763-6 (1974)

10.2 Clinical Laboratory Methods

RAPID RADIOIMMUNOASSAY OF TRIIODOTHYRONINE ON SEPHADEX G-25 BY THE AMES KIT. SERUM FROM 57 PATIENTS ANALYZED.
HOWORTH P, MARSDEN P; J NUCL MED 17 (APR): 321-2 (1976)
SIMULTANEOUS MEASUREMENT OF TRIIODOTHYRONINE & THYROXINE IN UNEXTRACTED SERUM SAMPLES USING A DOUBLE TRACER RADIOIMMUNOASSAY METHOD. COMBINED METHOD APPEARS TO BE ACCURATE, SENSITIVE, SPECIFIC, & TIME SAVING.
BROWN M ET AL; J NUCL MED 18 (MAR): 300-4 (1977)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (98.9%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (98.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (98.3%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 174 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Skin Irrit. 2 (98.9%)

Eye Irrit. 2A (98.9%)

STOT SE 3 (98.3%)

11.2 Accidental Release Measures

11.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

11.3 Handling and Storage

11.3.1 Storage Conditions

Commercially available liothyronine sodium tablets should be stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C. Commercially available liothyronine sodium injection should be stored at 2-8 °C. /Liothyronine sodium/
McEvoy, G.K. (ed.). American Hospital Formulary Service-Drug Information 19 98. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1998 (Plus Supplements)., p. 2646

11.4 Regulatory Information

11.4.1 FDA Requirements

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
21 CFR 200-299, 300-499, 820, and 860 (4/1/97)

11.5 Other Safety Information

Chemical Assessment

IMAP assessments - L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-: Environment tier I assessment

IMAP assessments - L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-: Human health tier I assessment

11.5.1 Special Reports

Hays MT; J Clin Endocrinol 63: 527 (1970). Absorption of triiodothyronine in man.
Surks MI, et al; J Clin Invest 52: 805 (1973). Determination of iodothyronine absorption and conversion to L-thyroxine (T4) to L-triiodothyronine (T3) using a rate turnover technique.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

The hormones, T4 and T3, are tyrosine-based hormones produced by the thyroid gland. Iodine is an important component in their synthesis. The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the more active liothyronine form by deiodinases in peripheral tissues. Liothyronine acts on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). The thyroid hormones are essential to proper development and differentiation of all cells of the human body. To various extents T4 and T3 regulate protein, fat and carbohydrate metabolism. Their most pronounced effect is on how human cells use energetic compounds. The thyroid hormone derivatives bind to the thyroid hormone receptors initially to initiate their downstream effects.

12.1.2 Drug Induced Liver Injury

Compound
liothyronine
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

12.1.3 Carcinogen Classification

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

12.1.4 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Liothyronine (T3) is a normal component of human milk. If replacement doses of liothyronine are required by the mother, it is not necessarily a reason to discontinue breastfeeding. However, because no information is available on the use of exogenous liothyronine during breastfeeding, an alternate drug may be preferred. The American Thyroid Association recommends that subclinical and overt hypothyroidism should be treated with levothyroxine in lactating women seeking to breastfeed. Liothyronine dosage requirement may be increased in the postpartum period compared to prepregnancy requirements patients with Hashimoto's thyroiditis.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date. However, the thyroid hormone content of human milk from the mothers of very preterm infants appears not to be sufficient to affect the infant’s thyroid status.

◉ Effects on Lactation and Breastmilk

Adequate thyroid hormone serum levels are required for normal lactation. Replacing deficient thyroid levels should improve milk production caused by hypothyroidism. Supraphysiologic doses of liothyronine would not be expected to further improve lactation.

12.1.5 Exposure Routes

95% in 4 hours

12.1.6 Acute Effects

12.1.7 Interactions

USE OF PROPRANOLOL IN CONJUNCTION WITH REPLACEMENT THERAPY HAS BEEN REPORTED TO DECR RISK OF ARRHYTHMIA & ANGINA...
American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 602
THYROID COMPOUNDS THAT PRODUCE HYPERMETABOLIC STATE (LIOTHYRONINE...) INCR RATE OF DECAY OF VITAMIN K-DEPENDENT CLOTTING FACTORS, & IN PRESENCE OF ORAL ANTICOAGULANTS /EG, WARFARIN/, NORMAL COMPENSATION BY INCR SYNTHESIS IS PREVENTED.
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 301
THERE IS CONSIDERABLE CLINICAL EVIDENCE THAT A PATIENT'S THYROID STATE AFFECTS RESPONSE TO TRICYCLIC ANTIDEPRESSANT DRUGS. ADDITION OF LIOTHYRONINE (25 UG/DAY) MAY PREVENT RELATIVELY LONG LAG TIME THAT OCCURS BEFORE CLINICAL EFFECTIVENESS OF TRICYCLIC ANTIDEPRESSANTS IS OBSERVED.
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 102
CHOLESTYRAMINE MAY CAUSE CLINICALLY SIGNIFICANT DECR IN ABSORPTION OF THYROID HORMONE WHEN THESE DRUGS ARE GIVEN SIMULTANEOUSLY. /THYROID HORMONE/
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 239
For more Interactions (Complete) data for LIOTHYRONINE (16 total), please visit the HSDB record page.

12.1.8 Human Toxicity Excerpts

UNTOWARD EFFECTS OF OVERDOSES OF THYROID HORMONES INCL TACHYCARDIA...ANGINA PECTORIS, HYPERTENSION...HYPERKINESIS...GI DISTURBANCES, & HYPOADRENOCORTICISM. ...MAY CAUSE ALLERGIC REACTIONS. /THYROID HORMONES/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 910
FRANKLY TOXIC DOSES INDUCE UNPLEASANT BUT TRANSIENT SYMPTOMS THAT RESEMBLE THYROTOXICOSIS (THYROID STORM). SIGNS & SYMPTOMS INCL PALPITATIONS, RAPID & IRREGULAR PULSE, HEADACHE, TREMORS, NERVOUSNESS, INSOMNIA, DELIRIUM, DIAPHORESIS, HYPERPYREXIA, VOMITING (SOMETIMES UNCONTROLLABLE), COLLAPSE & COMA. /THYROID/
Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-52
LOW TOXICITY @ NORMAL DOSAGE.
Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 885

12.1.9 Non-Human Toxicity Excerpts

IN RATS EXOPHTHALMOS HAS BEEN PRODUCED /BY USE OF LIOTHYRONINE/. IN RABBITS INTRAOCULAR PRESSURE HAS BEEN REDUCED 4 MM HG BY SUBCONJUNCTIVAL INJECTION OF TRIIODOTHYRONINE...
Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 1058
Four pregnant New Zealand white rabbits received intramuscular triiodothyronine (Liothyronine; T3) at 125 ug/kg on days 25 and 26 of gestation. Another group of 6 rabbits served as controls. Maternal and fetal plasma-free T3, thyroxine (T4), and glucose concentration, as well as fetal liver glycogen content, were evaluated on day 27 of gestation. In T3-treated rabbits, maternal and fetal plasma-free T3 concentration was higher than in controls. T3 treatment resulted in fetal hyperglycemia and depletion of fetal liver glycogen content.
Devaskar UP et al; Dev Pharmacol Ther 9:115-123 (1986)

12.1.10 Protein Binding

Liothyronine presents a very large binding to plasma proteins and around 99.7% of the administered dose can be found bound. Liothyronine is found to be bound to thyroxine-binding globulin, thyroxine-binding prealbumin and albumin. It is important to consider that only the little unbound portion of liothyronine is metabolically active.

12.2 Ecological Information

12.2.1 Milk Concentrations

Although only minimal amounts of thyroid hormones are distributed into milk. ... /Thyroid agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service-Drug Information 19 98. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1998 (Plus Supplements)., p. 2642

13 Associated Disorders and Diseases

Disease
Anorexia nervosa
References
Disease
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
References
Disease
Proprotein Convertase 1/3 Deficiency
References
PubMed: 7477119
Disease
Hyperthyroidism
References
Disease
Hypothyroidism
References

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Nature Journal References

14.7 Chemical Co-Occurrences in Literature

14.8 Chemical-Gene Co-Occurrences in Literature

14.9 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Drug-Food Interactions

Take with or without food.

16.5 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

Zebrafish Pathway Metabolite MetFrag Local CSV (Beta) | DOI:10.5281/zenodo.3457553
The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: Metabolite

19.5 KEGG: Target-based Classification of Drugs

19.6 KEGG: Drug Groups

19.7 FDA Pharm Classes

19.8 ChemIDplus

19.9 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.10 ChEMBL Target Tree

19.11 UN GHS Classification

19.12 NORMAN Suspect List Exchange Classification

19.13 CCSBase Classification

19.14 EPA DSSTox Classification

19.15 LOTUS Tree

19.16 EPA Substance Registry Services Tree

19.17 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-
    https://services.industrialchemicals.gov.au/search-assessments/
  2. CAS Common Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc/4.0/
    L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-, labeled with iodine-125
    https://commonchemistry.cas.org/detail?cas_rn=15785-49-6
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  6. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  7. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  8. Hazardous Substances Data Bank (HSDB)
  9. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  10. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
    (2R)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
    https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=18860
  11. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  12. Drug Gene Interaction database (DGIdb)
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    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  13. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  14. Therapeutic Target Database (TTD)
  15. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  16. Burnham Center for Chemical Genomics
  17. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  18. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Liothyronine
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  19. ChEBI
  20. E. coli Metabolome Database (ECMDB)
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    https://ecmdb.ca/citations
  21. FDA Pharm Classes
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  23. NCI Thesaurus (NCIt)
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    https://www.cancer.gov/policies/copyright-reuse
  24. Open Targets
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    https://platform-docs.opentargets.org/licence
  25. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  26. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  27. DailyMed
  28. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  29. Drugs and Lactation Database (LactMed)
  30. ECI Group, LCSB, University of Luxembourg
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    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Triiodothyronine
  31. Natural Product Activity and Species Source (NPASS)
  32. EU Clinical Trials Register
  33. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
    3,3',5-Triiodo-L-thyronine
    http://www.nist.gov/srd/nist1a.cfm
  34. SpectraBase
    2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt
    https://spectrabase.com/spectrum/16pAcismm6d
    2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt
    https://spectrabase.com/spectrum/GqbxcH6zzq9
  35. Japan Chemical Substance Dictionary (Nikkaji)
  36. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  37. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  38. MassBank Europe
  39. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  40. Metabolomics Workbench
  41. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  42. Nature Chemical Biology
  43. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  44. NMRShiftDB
  45. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  46. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  47. Protein Data Bank in Europe (PDBe)
  48. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  49. Springer Nature
  50. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  51. Wikidata
    3,3',5-triiodo-L-thyronine zwitterion
    https://www.wikidata.org/wiki/Q106345628
  52. Wikipedia
  53. Wiley
  54. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  55. PubChem
  56. GHS Classification (UNECE)
  57. EPA Substance Registry Services
  58. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  59. PATENTSCOPE (WIPO)
  60. NCBI
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