3,3',5,5'-TETRAIODOTHYROACETIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H8I4O4
Molecular Weight	747.8288
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of 3,3',5,5'-TETRAIODOTHYROACETIC ACID

Structure Search

SMILES

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

InChI

InChIKey=PPJYSSNKSXAVDB-UHFFFAOYSA-N

InChI=1S/C14H8I4O4/c15-8-4-7(5-9(16)13(8)21)22-14-10(17)1-6(2-11(14)18)3-12(19)20/h1-2,4-5,21H,3H2,(H,19,20)

HIDE SMILES / InChI

Molecular Formula	C14H8I4O4
Molecular Weight	747.8288
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19846915
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25628605 | https://www.ncbi.nlm.nih.gov/pubmed/19427201 | https://www.ncbi.nlm.nih.gov/pubmed/19381627 | https://www.drugbank.ca/drugs/DB01751

3,3',5,5'-Tetraiodothyroacetic acid (Tetrac) is a deaminated analog of L-thyroxine (T4) that blocks the proangiogenesis actions of T4 and 3, 5, 3’-triiodo-L-thyronine as well as other growth factors at the cell surface receptor for thyroid hormone on integrin αvβ3. 3,3',5,5'-Tetraiodothyroacetic acid blocks the transcriptional activities directed by L-thyroxine (T4) and 3,5,3’-triiodo-L-thyronine (T3) at αvβ3, but, independently of T4 and T3, 3,3',5,5'-Tetraiodothyroacetic acid modulates transcription of cancer cell genes that are important to cell survival pathways, control of the cell cycle, angiogenesis (VEGFA, FGF), apoptosis, cell export of chemotherapeutic agents, and repair of double-strand DNA breaks. 3,3',5,5'-Tetraiodothyroacetic acid was found to perturb the angiogenesis process stimulated by VEGF (Vascular Endothelial Growth Factor) or FGF (Fibroblast Growth Factor) without influencing the preexisting blood vessels.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-V/beta-3 8 Target ID: CHEMBL1907598 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25628605	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ovarian cancer 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29184090	Primary		Basic research	Unknown Approved Use Unknown
Myeloma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29018054	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Differences between the effects of thyroxine and tetraiodothyroacetic acid on TSH suppression and cardiac hypertrophy.	2001 Feb	11182751
Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs.	2002 May	12010632
Disparate effects of thyroid hormone on actions of epidermal growth factor and transforming growth factor-alpha are mediated by 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase II.	2004 Apr	14691008
Putative L-triiodothyronine receptors in the liver nuclei of mature tropical toad, Bufo melanostictus.	2004 Jan-Feb	15018064
Thyroid hormone causes mitogen-activated protein kinase-dependent phosphorylation of the nuclear estrogen receptor.	2004 Jul	15059947
Proangiogenic action of thyroid hormone is fibroblast growth factor-dependent and is initiated at the cell surface.	2004 Jun 11	15117822
T-Screen as a tool to identify thyroid hormone receptor active compounds.	2005 Feb	21783481
Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis.	2005 Jul	15802494
Acetylation of nuclear hormone receptor superfamily members: thyroid hormone causes acetylation of its own receptor by a mitogen-activated protein kinase-dependent mechanism.	2005 May-Jun	15862828
Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution.	2005 Oct	16204882
The proangiogenic action of thyroid hormone analogue GC-1 is initiated at an integrin.	2005 Sep	16116342
Proangiogenesis action of the thyroid hormone analog 3,5-diiodothyropropionic acid (DITPA) is initiated at the cell surface and is integrin mediated.	2006 Apr	16384862
Pro-angiogenesis action of thyroid hormone and analogs in a three-dimensional in vitro microvascular endothelial sprouting model.	2006 Dec	17164749
Acting via a cell surface receptor, thyroid hormone is a growth factor for glioma cells.	2006 Jul 15	16849576
Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery.	2007	17727706
Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic.	2007 Feb	17174366
Molecular modeling of the thyroid hormone interactions with alpha v beta 3 integrin.	2007 Feb	17166537
Tetraiodothyroacetic acid, a small molecule integrin ligand, blocks angiogenesis induced by vascular endothelial growth factor and basic fibroblast growth factor.	2008	18080776
Stability indicating validated HPLC method for quantification of levothyroxine with eight degradation peaks in the presence of excipients.	2008 Aug 6	18524511
Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated.	2008 Jan	17984113
Sensory neuron sodium current requires nongenomic actions of thyroid hormone during development.	2008 Nov	18799597
Cytoplasm-to-nucleus shuttling of thyroid hormone receptor-beta1 (Trbeta1) is directed from a plasma membrane integrin receptor by thyroid hormone.	2009	19557589
Radiosensitization of GL261 glioma cells by tetraiodothyroacetic acid (tetrac).	2009 Aug 15	19597333
Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor.	2009 Dec	19755667
Semisynthesis and pharmacological activities of Tetrac analogs: angiogenesis modulators.	2009 Jun 15	19427201
L-Thyroxine vs. 3,5,3'-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase.	2009 May	19158403
Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac).	2009 Nov 1	19838061
Tetraidothyroacetic acid (tetrac) and tetrac nanoparticles inhibit growth of human renal cell carcinoma xenografts.	2009 Oct	19846915
Protective effect of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraiodothyroacetic acids on serum albumin fibrillation.	2009 Sep	19381627
Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid.	2010 Apr	20133461
Mini-review: Cell surface receptor for thyroid hormone and nongenomic regulation of ion fluxes in excitable cells.	2010 Feb 9	19248795
Active metabolism of thyroid hormone during metamorphosis of amphioxus.	2010 Jul	21558188
Human platelet aggregation and degranulation is induced in vitro by L-thyroxine, but not by 3,5,3'-triiodo-L-thyronine or diiodothyropropionic acid (DITPA).	2010 Jun	19903697
Tetraiodothyroacetic acid and tetraiodothyroacetic acid nanoparticle effectively inhibit the growth of human follicular thyroid cell carcinoma.	2010 Mar	20187783
Thyroid hormone and angiogenesis.	2010 Mar-Apr	19879961
Thyroid hormones induce activation of rat hepatic stellate cells through increased expression of p75 neurotrophin receptor and direct activation of Rho.	2010 May	20231820
Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8.	2010 Sep 3	20628049
Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism.	2012 Feb 15	22227104

Patents

Sample Use Guides

In Vivo Use Guide

Mice were treated with daily injection of tetrac (400 ng/g body weight) during the first postnatal week

Route of Administration: Intravenous

In Vitro Use Guide

RCC renal cell carcinoma (RCC) were grown in RPMI-1640 medium (Invitrogen, Grand Island, NY, USA) supplemented with 10% FCS (Atlanta Biologicals, Lawrenceville, GA, USA). Penicillin/streptomycin (1%) was present in both culture media. The cells were trypsinized, centrifuged, and the cell pellet was re-suspended in the corresponding media. Subsequently, 500 μl of the suspension (~50,000 cells) were transferred to each well of a 4-well glass slide, Chamber slide System (Nalge Nunc International, Naperville, IL, USA) and incubated for 24 h at 37˚C with 5% CO2 (Thermo Electron Corp., Forma Series II). The cells were treated with 20 μl of each free Tetrac tagged with Cy3 dye and PLGA-Tetrac tagged with Cy3 separately incubated (37˚C, 5% CO2) for around 2 h. After 2 h of incubation, the plates were taken out and washed several times with PBS and then fixed in 1% formaldehyde (Sigma), and mounted with the help of Vectashield (Vector Laboratories Inc, Burlingame, CA, USA.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:14:57 GMT 2023` Edited by `admin` on `Fri Dec 15 19:14:57 GMT 2023`
Record UNII	PA7UX1FFYQ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

3,3',5,5'-TETRAIODOTHYROACETIC ACID

Common Name

English

LIOTHYRONINE SODIUM IMPURITY D [EP IMPURITY]

Common Name

English

T4-ACETIC ACID

Common Name

English

ACETIC ACID, (4-(4-HYDROXY-3,5-DIIODOPHENOXY)-3,5-DIIODOPHENYL)-

Common Name

English

TETRAC

Common Name

English

LEVOTHYROXINE SODIUM IMPURITY D [EP IMPURITY]

Common Name

English

TETRAIODOTHYROACETIC ACID

Common Name

English

LEVOTHYROXINE SODIUM IMPURITY, T4-ACETIC ACID- [USP IMPURITY]

Common Name

English

THYROACETIC ACID, 3,3',5,5'-TETRAIODO-

Common Name

English

(4-(4-HYDROXY-3,5-DIIODOPHENOXY)-3,5-DIIODOPHENYL)ACETIC ACID

Systematic Name

English

BENZENEACETIC ACID, 4-(4-HYDROXY-3,5-DIIODOPHENOXY)-3,5-DIIODO-

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

485115