Liothyronine
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Basic Info
| Common Name | Liothyronine(F05499) |
| 2D Structure | |
| Description | The L-triiodothyronine (T<sub>3</sub>, liothyronine) thyroid hormone is normally synthesized and secreted by the thyroid gland in much smaller quantities than L-tetraiodothyronine (T<sub>4</sub>, levothyroxine, L-thyroxine). Most T3 is derived from peripheral monodeiodination of T4 at the 5 position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3. |
| FRCD ID | F05499 |
| CAS Number | 6893-02-3 |
| PubChem CID | 5920 |
| Formula | C15H12I3NO4 |
| IUPAC Name | (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid |
| InChI Key | AUYYCJSJGJYCDS-LBPRGKRZSA-N |
| 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 |
| Canonical SMILES | C1=CC(=C(C=C1OC2=C(C=C(C=C2I)CC(C(=O)O)N)I)I)O |
| Isomeric SMILES | C1=CC(=C(C=C1OC2=C(C=C(C=C2I)C[C@@H](C(=O)O)N)I)I)O |
| Wikipedia | Liothyronine |
| Synonyms |
liothyronine
triiodothyronine
3,3',5-Triiodo-L-thyronine
6893-02-3
Liothyronin
Tresitope
3,5,3'-triiodothyronine
L-Liothyronine
triothyrone
Liothyroninum
|
| Classifies |
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Amino acids, peptides, and analogues |
| Intermediate Tree Nodes | Amino acids and derivatives - Alpha amino acids and derivatives |
| Direct Parent | Phenylalanine and derivatives |
| Alternative Parents |
|
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Phenylalanine or derivatives - Diphenylether - Diaryl ether - 3-phenylpropanoic-acid - Alpha-amino acid - Amphetamine or derivatives - L-alpha-amino acid - Phenoxy compound - 2-iodophenol - 2-halophenol - Phenol ether - Iodobenzene - 1-hydroxy-2-unsubstituted benzenoid - Halobenzene - Phenol - Aralkylamine - Aryl iodide - Aryl halide - Monocyclic benzene moiety - Benzenoid - Amino acid - Ether - Carboxylic acid - Monocarboxylic acid or derivatives - Organic nitrogen compound - Primary aliphatic amine - Organohalogen compound - Organoiodide - Organonitrogen compound - Organooxygen compound - Primary amine - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organic oxygen compound - Amine - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 650.977 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Complexity | 402 |
| Monoisotopic Mass | 650.79 |
| Exact Mass | 650.79 |
| XLogP | 1.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 23 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.6886 |
| Human Intestinal Absorption | HIA+ | 0.7212 |
| Caco-2 Permeability | Caco2- | 0.6530 |
| P-glycoprotein Substrate | Non-substrate | 0.5321 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9175 |
| Non-inhibitor | 0.9709 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8891 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6085 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8309 |
| CYP450 2D6 Substrate | Non-substrate | 0.9116 |
| CYP450 3A4 Substrate | Non-substrate | 0.6847 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.5924 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7037 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9230 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8310 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8459 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9697 |
| Non-inhibitor | 0.8508 | |
| AMES Toxicity | Non AMES toxic | 0.7591 |
| Carcinogens | Non-carcinogens | 0.9148 |
| Fish Toxicity | High FHMT | 0.9850 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9891 |
| Honey Bee Toxicity | Low HBT | 0.5811 |
| Biodegradation | Not ready biodegradable | 0.9693 |
| Acute Oral Toxicity | III | 0.7657 |
| Carcinogenicity (Three-class) | Non-required | 0.6124 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -5.1574 | LogS |
| Caco-2 Permeability | -0.0976 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.7082 | LD50, mol/kg |
| Fish Toxicity | 0.3755 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.9420 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Type of sweet flavour carrier affects thyroid axis activity in male rats. | Eur J Nutr | 2018 Mar | 28040879 |
| Comparison of triadimefon and its metabolite on acute toxicity and chronic effects during the early development of Rana nigromaculata tadpoles. | Ecotoxicol Environ Saf | 2018 Jul 30 | 29554609 |
| Interrelationship between iodine nutritional status of lactating mothers andtheir absolutely breast-fed infants in coastal districts of Gangetic West Bengal in India. | Eur J Pediatr | 2018 Jan | 29063209 |
| Maternal betaine administration modulates hepatic type 1 iodothyronine deiodinase(Dio1) expression in chicken offspring through epigenetic modifications. | Comp Biochem Physiol B Biochem Mol Biol | 2018 Apr | 29452261 |
| Dietary Supplementation of Chromium Can Alleviate Negative Impacts of Heat Stresson Performance, Carcass Yield, and Some Blood Hematology and Chemistry Indices ofGrowing Japanese Quail. | Biol Trace Elem Res | 2017 Sep | 28097602 |
| Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction andn-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats. | Nutrients | 2017 Oct 19 | 29048374 |
| Effect of dietary utilisation of sugarcane press mud on production performance ofMuzaffarnagari lambs. | Trop Anim Health Prod | 2017 Oct | 28677034 |
| Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism andHyperthyroidism: The Relation to Zinc. | Biochem Genet | 2017 Jun | 28097455 |
| Factors related to endocrine changes and hormone substitution treatment duringpre- and post-operation stages in craniopharyngioma. | Oncol Lett | 2017 Jan | 28123549 |
| Somatostatin Agonist Pasireotide Inhibits Exercise-Stimulated Growth in the Male Siberian Hamster (Phodopus sungorus). | J Neuroendocrinol | 2017 Jan | 27874965 |
| Effects of arsenic supplementation in feed on laying performance, arsenic retention of eggs and organs, biochemical indices and endocrine hormones. | Br Poult Sci | 2017 Feb | 27636676 |
| Effects of selenium supplementation on the oxidative state of acute heatstress-exposed quails. | J Anim Physiol Anim Nutr (Berl) | 2017 Feb | 26849471 |
| Preparation for radioactive iodine therapy is not a risk factor for thedevelopment of hyponatremia in thyroid cancer patients. | Medicine (Baltimore) | 2017 Feb | 28151897 |
| Approaches for grouping of pesticides into cumulative assessment groups for risk assessment of pesticide residues in food. | Regul Toxicol Pharmacol | 2017 Feb | 27965130 |
| Propolis supplementation attenuates the negative effects of oxidative stressinduced by paraquat injection on productive performance and immune function inturkey poults. | Poult Sci | 2017 Dec 1 | 29053856 |
| Thyroid disrupting effects of halogenated and next generation chemicals on theswim bladder development of zebrafish. | Aquat Toxicol | 2017 Dec | 29101780 |
| Polychlorinated Biphenyl-Related Alterations of the Expression of Essential Genesin Harbour Seals (Phoca vitulina) from Coastal Sites in Canada and the UnitedStates. | Arch Environ Contam Toxicol | 2017 Aug | 28528409 |
| Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of AutoimmuneThyroid Target Sites with Dietary Proteins. | J Thyroid Res | 2017 | 28894619 |
| Widespread occurrence of perchlorate in water, foodstuffs and human urinecollected from Kuwait and its contribution to human exposure. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2016Jun | 27248576 |
| Effects of sodium butyrate supplementation on reproductive performance andcolostrum composition in gilts. | Animal | 2016 Oct | 27040131 |
Targets
- 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 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Alpha-2: Does not bind thyroid hormone and functions as a weak dominant negative inhibitor of thyroid hormone action.
- Gene Name:
- THRA
- Uniprot ID:
- P10827
- Molecular Weight:
- 54815.055 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Purine nucleoside binding
- Specific Function:
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name:
- ADORA1
- Uniprot ID:
- P30542
- Molecular Weight:
- 36511.325 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
- Gene Name:
- PGR
- Uniprot ID:
- P06401
- Molecular Weight:
- 98979.96 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Protein tyrosine/serine/threonine phosphatase activity
- Specific Function:
- Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.
- Gene Name:
- DUSP3
- Uniprot ID:
- P51452
- Molecular Weight:
- 20478.1 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
- Gene Name:
- HTR6
- Uniprot ID:
- P50406
- Molecular Weight:
- 46953.625 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
- Gene Name:
- NR3C1
- Uniprot ID:
- P04150
- Molecular Weight:
- 85658.57 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.
- Gene Name:
- MMP13
- Uniprot ID:
- P45452
- Molecular Weight:
- 53819.32 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]