T3DB: Tetrabromobisphenol A

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (14)XML

Targets (14)

Record Information

Version

2.0

Creation Date

2009-06-22 16:08:38 UTC

Update Date

2014-12-24 20:24:39 UTC

Accession Number

T3D1803

Identification

Common Name

Tetrabromobisphenol A

Class

Small Molecule

Description

Tetrabromobisphenol A is an organobromide compound and a brominated flame retardant. In the reactive application, TBBPA is bound chemically to the polymers. The main use is epoxy resins of printed circuit boards. As an additive flame retardant it is used in acrylonitrile butadiene styrene, which is found in products such as TVs. Bromine is a halogen element with the symbol Br and atomic number 35. Diatomic bromine does not occur naturally, but bromine salts can be found in crustal rock. (4, 7)

Compound Type

Bromide Compound
Industrial/Workplace Toxin
Organic Compound
Organobromide
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2, 2-Bis(3,5-dibromo-4-hydroxyphenyl)propane
2,2',6,6'-Tetrabromo-4,4'-isopropylidene phenol
2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol
2,2',6,6'-Tetrabromobisphenol A
2,2-Bis(3,5-dibromo-4-hydroxyphenyl)propane
2,2-Bis(4-hydroxy-3, 5-dibromophenyl)propane
2,2-Bis(4-hydroxy-3,5-dibromophenyl)propane
3,3',5,5'-Tetrabromo bisphenol A
3,3',5,5'-TETRABROMO-4,4-DIHYDROXY-2,-2-DIPHENYLPROPANE
3,3',5,5'-Tetrabromo-4,4-dihydroxy-2,2-diphenylpropane
3,3',5,5'-Tetrabromobisphenol A
3,5,3', 5'-Tetrabromobisphenol A
3,5,3',5'-Tetrabromobisphenol A
4,4'-(1-Methylethylidene)bis(2,6-dibromophenol)
4,4'-(1-Methylethylidene)bisphenol tetrabromo deriv.
4,4'-(2,2-propanediyl) bis[2,6-dibromo]phenol
4,4'-(propane-2,2-diyl)bis(2,6-dibromophenol)
4,4'-isopropylidene-bis(2,6-dibromophenol)
4,4'-Isopropylidenebis(2, 6-dibromophenol)
4,4'-Isopropylidenebis(2,6-dibromophenol)
4,4'-Isopropylylidenebis(2,6-dibromophenol)
4,4'-Osopropylidenebis (2,6-dibromophenol)
4,4'-propane-2,2-diylbis(2,6-dibromophenol)
Bromdian
Fire Guard 2000
Firemaster BP 4A
Firemaster BP4A
Great lakes BA-59P
Phenol, 4, {4'-(1-methylethylidene)bis[2,6-dibromo-}
Phenol, 4, {4'-isopropylidenebis[2,6-dibromo-}
Phenol, 4,4'-(1-methylethylidene)bis-, tetrabromo deriv.
phenol, 4,4'-isopropylidenebis (dibromo-)
Phenol, 4,4'-isopropylidenebis(2,6-dibromo- (8CI)
Saytex RB 100PC
Saytex RB-100
Saytex RB-100 ABS
Tbbpa CPD
Tetrabromobisphenol a
Tetrabromodian
Tetrabromodiphenylopropane

Chemical Formula

C₁₅H₁₂Br₄O₂

Average Molecular Mass

543.871 g/mol

Monoisotopic Mass

539.757 g/mol

CAS Registry Number

79-94-7

IUPAC Name

2,6-dibromo-4-[2-(3,5-dibromo-4-hydroxyphenyl)propan-2-yl]phenol

Traditional Name

tetrabromobisphenol A

SMILES

CC(C)(C1=CC(Br)=C(O)C(Br)=C1)C1=CC(Br)=C(O)C(Br)=C1

InChI Identifier

InChI=1S/C15H12Br4O2/c1-15(2,7-3-9(16)13(20)10(17)4-7)8-5-11(18)14(21)12(19)6-8/h3-6,20-21H,1-2H3

InChI Key

InChIKey=VEORPZCZECFIRK-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as bisphenols. These are methylenediphenols, HOC6H4CH2C6H4OH, commonly p,p-methylenediphenol, and their substitution products (generally derived from condensation of two equivalent amounts of a phenol with an aldehyde or ketone).

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Diphenylmethanes

Direct Parent

Bisphenols

Alternative Parents

Substituents

Bisphenol
Phenylpropane
2-bromophenol
2-halophenol
Phenol
Halobenzene
Bromobenzene
Aryl halide
Aryl bromide
Organic oxygen compound
Hydrocarbon derivative
Organooxygen compound
Organobromide
Organohalogen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

bromobisphenol (CHEBI:33217 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

flame retardant

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	181°C
Boiling Point	250°C (decomposes)
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00041 g/L	ALOGPS
logP	6.57	ALOGPS
logP	7.12	ChemAxon
logS	-6.1	ALOGPS
pKa (Strongest Acidic)	6.57	ChemAxon
pKa (Strongest Basic)	-7.4	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	40.46 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	109.77 m³·mol⁻¹	ChemAxon
Polarizability	38.92 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	splash10-0006-0000090000-c6aa46e307361b5d536f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0006-0010090000-7f25bf8be57da097f541	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-01vo-0080490000-1252493d1ec4e0a3c094	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0000090000-2875599193d092b60326	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000i-0000090000-cbdf053803c92889c114	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-000b-0090080000-0d129e3657f53c844da6	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-004i-5960080000-bf799dadde651af9c9ac	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100.40 MHz, DMSO-d6, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Oral (5) ; inhalation (5) ; dermal (5)

Mechanism of Toxicity

Bromine is a powerful oxidizing agent and is able to release oxygen free radicals from the water in mucous membranes. These free radicals are also potent oxidizers and produce tissue damage. In additon, the formation of hydrobromic and bromic acids will result in secondary irritation. The bromide ion is also known to affect the central nervous system, causing bromism. This is believed to be a result of bromide ions substituting for chloride ions in the in actions of neurotransmitters and transport systems, thus affecting numerous synaptic processes. (5, 6, 1)

Metabolism

Bromine is mainly absorbed via inhalation, but may also enter the body through dermal contact. Bromine salts can be ingested. Due to its reactivity, bromine quickly forms bromide and may be deposited in the tissues, displacing other halogens. (5)

Toxicity Values

LD50: >5 g/kg (Oral, Rat) (2) LD50: >2 g/kg (Dermal, Rabbit) (2)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

Not Available

Minimum Risk Level

Not Available

Health Effects

Bromine vapour causes irritation and direct damage to the mucous membranes. Elemental bromine also burns the skin. The bromide ion is a central nervous system depressant and chronic exposure produces neuronal effects. This is called bromism and can result in central reactions reaching from somnolence to coma, cachexia, exicosis, loss of reflexes or pathologic reflexes, clonic seizures, tremor, ataxia, loss of neural sensitivity, paresis, papillar edema of the eyes, abnormal speech, cerebral edema, delirium, aggressiveness, and psychoses. (4, 5, 6)

Symptoms

Bromine vapour causes irritation and direct damage to the mucous membranes. Symptoms include lacrimation, rhinorrhoea, eye irritation with mucous secretions from the oropharyngeal and upper airways, coughing, dyspnoea, choking, wheezing, epistaxis, and headache. The bromide ion is a central nervous system depressant producing ataxia, slurred speech, tremor, nausea, vomiting, lethargy, dizziness, visual disturbances, unsteadiness, headaches, impaired memory and concentration, disorientation and hallucinations. This is called bromism. (5, 6)

Treatment

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

33217

BioCyc ID

CPD-10489

CTD ID

C020806

Stitch ID

Tetrabromobisphenol A

PDB ID

Not Available

ACToR ID

3324

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D1803.pdf

General References

Ziouzenkova O, Orasanu G, Sharlach M, Akiyama TE, Berger JP, Viereck J, Hamilton JA, Tang G, Dolnikowski GG, Vogel S, Duester G, Plutzky J: Retinaldehyde represses adipogenesis and diet-induced obesity. Nat Med. 2007 Jun;13(6):695-702. Epub 2007 May 27. [17529981 ]
Clayton GD and Clayton FE (eds) (1993-1994). Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc.
Golomb, BA (1999). A Review of the Scientific Literature As It Pertains to Gulf War Illnesses. Volume 2: Pyridostigmine Bromide. Washington, DC: RAND.
Wikipedia. Bromine. Last Updated 9 June 2009. [Link]
International Programme on Chemical Safety (IPCS) INCHEM (1992). Poison Information Monograph for Bromine. [Link]
Wikipedia. Potassium bromide. Last Updated 9 June 2009. [Link]
Wikipedia. Tetrabromobisphenol A. Last Updated 30 April 2009. [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Not Available

Targets

Target Details

1. Peroxisome proliferator-activated receptor gamma

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:: PPARG
Uniprot ID:: P37231
Molecular Weight:: 57619.58 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.02 uM	NVS_NR_hPPARg	Novascreen
AC50	0.33 uM	Tox21_PPARg_BLA_Agonist_ratio	Tox21/NCGC

References

Riu A, Grimaldi M, le Maire A, Bey G, Phillips K, Boulahtouf A, Perdu E, Zalko D, Bourguet W, Balaguer P: Peroxisome proliferator-activated receptor gamma is a target for halogenated analogs of bisphenol A. Environ Health Perspect. 2011 Sep;119(9):1227-32. doi: 10.1289/ehp.1003328. Epub 2011 May 11. [21561829 ]
Riu A, le Maire A, Grimaldi M, Audebert M, Hillenweck A, Bourguet W, Balaguer P, Zalko D: Characterization of novel ligands of ERalpha, Erbeta, and PPARgamma: the case of halogenated bisphenol A and their conjugated metabolites. Toxicol Sci. 2011 Aug;122(2):372-82. doi: 10.1093/toxsci/kfr132. Epub 2011 May 27. [21622942 ]
Suzuki G, Tue NM, Malarvannan G, Sudaryanto A, Takahashi S, Tanabe S, Sakai S, Brouwer A, Uramaru N, Kitamura S, Takigami H: Similarities in the endocrine-disrupting potencies of indoor dust and flame retardants by using human osteosarcoma (U2OS) cell-based reporter gene assays. Environ Sci Technol. 2013 Mar 19;47(6):2898-908. doi: 10.1021/es304691a. Epub 2013 Mar 1. [23398518 ]
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 ]

Target Details

2. Progesterone receptor

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

Li J, Ma M, Wang Z: In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16. [19765641 ]
Suzuki G, Tue NM, Malarvannan G, Sudaryanto A, Takahashi S, Tanabe S, Sakai S, Brouwer A, Uramaru N, Kitamura S, Takigami H: Similarities in the endocrine-disrupting potencies of indoor dust and flame retardants by using human osteosarcoma (U2OS) cell-based reporter gene assays. Environ Sci Technol. 2013 Mar 19;47(6):2898-908. doi: 10.1021/es304691a. Epub 2013 Mar 1. [23398518 ]

Target Details

3. Androgen receptor

General Function:: Zinc ion binding
Specific Function:: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:: AR
Uniprot ID:: P10275
Molecular Weight:: 98987.9 Da

References

Suzuki G, Tue NM, Malarvannan G, Sudaryanto A, Takahashi S, Tanabe S, Sakai S, Brouwer A, Uramaru N, Kitamura S, Takigami H: Similarities in the endocrine-disrupting potencies of indoor dust and flame retardants by using human osteosarcoma (U2OS) cell-based reporter gene assays. Environ Sci Technol. 2013 Mar 19;47(6):2898-908. doi: 10.1021/es304691a. Epub 2013 Mar 1. [23398518 ]

Target Details

4. Arachidonate 12-lipoxygenase, 12S-type

General Function:: Oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
Specific Function:: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Mainly converts arachidonic acid to (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation.
Gene Name:: ALOX12
Uniprot ID:: P18054
Molecular Weight:: 75693.38 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	10 uM	Not Available	BindingDB 50150793

References

Segraves EN, Shah RR, Segraves NL, Johnson TA, Whitman S, Sui JK, Kenyon VA, Cichewicz RH, Crews P, Holman TR: Probing the activity differences of simple and complex brominated aryl compounds against 15-soybean, 15-human, and 12-human lipoxygenase. J Med Chem. 2004 Jul 29;47(16):4060-5. [15267244 ]

Target Details

5. Arachidonate 15-lipoxygenase

General Function:: Phosphatidylinositol-4,5-bisphosphate binding
Specific Function:: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid into 12-hydroperoxyeicosatetraenoic acid/12-HPETE and 15-hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass.
Gene Name:: ALOX15
Uniprot ID:: P16050
Molecular Weight:: 74803.795 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	4 uM	Not Available	BindingDB 50150793

References

Segraves EN, Shah RR, Segraves NL, Johnson TA, Whitman S, Sui JK, Kenyon VA, Cichewicz RH, Crews P, Holman TR: Probing the activity differences of simple and complex brominated aryl compounds against 15-soybean, 15-human, and 12-human lipoxygenase. J Med Chem. 2004 Jul 29;47(16):4060-5. [15267244 ]

Target Details

6. Estrogen receptor

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

Suzuki G, Tue NM, Malarvannan G, Sudaryanto A, Takahashi S, Tanabe S, Sakai S, Brouwer A, Uramaru N, Kitamura S, Takigami H: Similarities in the endocrine-disrupting potencies of indoor dust and flame retardants by using human osteosarcoma (U2OS) cell-based reporter gene assays. Environ Sci Technol. 2013 Mar 19;47(6):2898-908. doi: 10.1021/es304691a. Epub 2013 Mar 1. [23398518 ]

Target Details

7. Nuclear receptor subfamily 1 group I member 2

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:: NR1I2
Uniprot ID:: O75469
Molecular Weight:: 49761.245 Da

References

Molina-Molina JM, Amaya E, Grimaldi M, Saenz JM, Real M, Fernandez MF, Balaguer P, Olea N: In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):127-36. doi: 10.1016/j.taap.2013.05.015. Epub 2013 May 25. [23714657 ]

Target Details

8. Thyroid hormone receptor alpha

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

Fini JB, Riu A, Debrauwer L, Hillenweck A, Le Mevel S, Chevolleau S, Boulahtouf A, Palmier K, Balaguer P, Cravedi JP, Demeneix BA, Zalko D: Parallel biotransformation of tetrabromobisphenol A in Xenopus laevis and mammals: Xenopus as a model for endocrine perturbation studies. Toxicol Sci. 2012 Feb;125(2):359-67. doi: 10.1093/toxsci/kfr312. Epub 2011 Nov 15. [22086976 ]

Target Details

9. Transthyretin

General Function:: Identical protein binding
Specific Function:: Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Gene Name:: TTR
Uniprot ID:: P02766
Molecular Weight:: 15886.88 Da

References

Meerts IA, van Zanden JJ, Luijks EA, van Leeuwen-Bol I, Marsh G, Jakobsson E, Bergman A, Brouwer A: Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicol Sci. 2000 Jul;56(1):95-104. [10869457 ]

Target Details

10. Cytochrome P450 2C19

General Function:: Steroid hydroxylase activity
Specific Function:: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:: CYP2C19
Uniprot ID:: P33261
Molecular Weight:: 55930.545 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.40 uM	NVS_ADME_hCYP2C19	Novascreen

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 ]

Target Details

11. Glucocorticoid receptor

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.81 uM	NVS_NR_hGR	Novascreen

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 ]

Target Details

12. Cytochrome P450 2C9

General Function:: Steroid hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular Weight:: 55627.365 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	2.79 uM	NVS_ADME_hCYP2C9	Novascreen

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 ]

Target Details

13. Nuclear factor erythroid 2-related factor 2

General Function:: Transcriptional activator activity, rna polymerase ii distal enhancer sequence-specific binding
Specific Function:: Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.
Gene Name:: NFE2L2
Uniprot ID:: Q16236
Molecular Weight:: 67825.9 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	6.45 uM	ATG_NRF2_ARE_CIS	Attagene

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 ]

Target Details

14. Peroxisome proliferator-activated receptor alpha

General Function:: Zinc ion binding
Specific Function:: Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Gene Name:: PPARA
Uniprot ID:: Q07869
Molecular Weight:: 52224.595 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	7.82 uM	NVS_NR_hPPARa	Novascreen

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 ]

Tetrabromobisphenol A (T3D1803)

Structure for T3D1803: Tetrabromobisphenol A

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