Tmic
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Record Information
Version2.0
Creation Date2014-08-12 17:18:06 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3946
Identification
Common Name4-Tert-octylphenol
ClassSmall Molecule
Descriptionalpha-(p-(1,1,3,3-Tetramethylbutyl)phenyl)-omega-hydroxypoly(oxyethylene) is used as a food additive [EAFUS] (EAFUS: Everything Added to Food in the United States. [http://www.eafus.com/]). alpha-(p-(1,1,3,3-Tetramethylbutyl)phenyl)-omega-hydroxypoly(oxyethylene) belongs to the family of p-Menthane Monoterpenes. These are monoterpenes whose structure is based on the p-menthane backbone.
Compound Type
  • Food Additive
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4-(1,1,3,3-Tetramethylbutyl)-Phenol
4-(1,1,3,3-Tetramethylbutyl)phenol
4-t-Octylphenol
p-(1',1',3', 3'-Tetramethylbutyl)phenol
p-(1',1',3',3'-Tetramethylbutyl)fenol
p-(1',1',3',3'-Tetramethylbutyl)phenol
p-(1,1,3,3-Tetramethylbutyl)-Phenol
p-(1,1,3,3-Tetramethylbutyl)phenol
p-(Tert-octyl)-Phenol
P-Octylphenol
P-Terc.oktylfenol
P-Tert-octylphenol
Para-tert-octylphenol
Tert-octylphenol, flaked
Chemical FormulaC14H22O
Average Molecular Mass206.324 g/mol
Monoisotopic Mass206.167 g/mol
CAS Registry Number140-66-9
IUPAC Name4-(2,4,4-trimethylpentan-2-yl)phenol
Traditional Name4-tert-octylphenol
SMILESCC(C)(C)CC(C)(C)C1=CC=C(O)C=C1
InChI IdentifierInChI=1S/C14H22O/c1-13(2,3)10-14(4,5)11-6-8-12(15)9-7-11/h6-9,15H,10H2,1-5H3
InChI KeyInChIKey=ISAVYTVYFVQUDY-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropanes
Direct ParentPhenylpropanes
Alternative Parents
Substituents
  • Phenylpropane
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cell junction
  • Extracellular
  • Membrane
  • Microsome
  • Mitochondrion
  • Peroxisome
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
TetracyclinesNot AvailableNot Available
QuinolonesNot AvailableNot Available
Ovarian SteroidogenesisNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point84.5°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.026 g/LALOGPS
logP5.29ALOGPS
logP4.69ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)10.23ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.93 m³·mol⁻¹ChemAxon
Polarizability24.96 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-2900000000-f92b122dd7da7c354da1View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0a4i-2190000000-c49bfd01ea946c72fc2eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0190000000-312caab5fa71d0dbc4acView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1590000000-554843e16a1b867f1463View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052s-5900000000-e546135869e4f5ba7231View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0090000000-b410576bf25ec1ab460fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0090000000-1705cc32a155c97241fbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0abi-4930000000-b11aff47964eb8485919View in MoNA
MSMass Spectrum (Electron Ionization)splash10-000i-3900000000-e0acd3551aaaeb8bc0a2View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB32528
PubChem Compound ID8814
ChEMBL IDCHEMBL259327
ChemSpider ID8483
KEGG IDC14205
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. 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 ]
  2. EAFUS: Everything Added to Food in the United States.
  3. Centers of Disease Control and Preventiion - Biomonitoring Summary for 4-tert-Octylphenol [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.22 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC505.83 uMATG_ERa_TRANSAttagene
AC502.82 uMATG_ERE_CISAttagene
AC502.70 uMNVS_NR_hERNovascreen
AC503.29 uMOT_ER_ERaERa_0480Odyssey Thera
AC504.37 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.41 uMOT_ERa_EREGFP_0120Odyssey Thera
AC500.56 uMOT_ERa_EREGFP_0480Odyssey Thera
AC504.52 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC501.09 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
References
  1. Yoon K, Pallaroni L, Stoner M, Gaido K, Safe S: Differential activation of wild-type and variant forms of estrogen receptor alpha by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements. J Steroid Biochem Mol Biol. 2001 Jul;78(1):25-32. [11530281 ]
  2. Nose T, Tokunaga T, Shimohigashi Y: Exploration of endocrine-disrupting chemicals on estrogen receptor alpha by the agonist/antagonist differential-docking screening (AADS) method: 4-(1-adamantyl)phenol as a potent endocrine disruptor candidate. Toxicol Lett. 2009 Dec 1;191(1):33-9. doi: 10.1016/j.toxlet.2009.08.001. Epub 2009 Aug 8. [19666091 ]
  3. 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. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.79 uMOT_ER_ERaERb_0480Odyssey Thera
AC503.10 uMOT_ER_ERaERb_1440Odyssey Thera
AC500.94 uMOT_ER_ERbERb_0480Odyssey Thera
AC501.28 uMOT_ER_ERbERb_1440Odyssey Thera
References
  1. Routledge EJ, White R, Parker MG, Sumpter JP: Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) alpha and ERbeta. J Biol Chem. 2000 Nov 17;275(46):35986-93. [10964929 ]
  2. Paris F, Balaguer P, Terouanne B, Servant N, Lacoste C, Cravedi JP, Nicolas JC, Sultan C: Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines. Mol Cell Endocrinol. 2002 Jul 31;193(1-2):43-9. [12161000 ]
  3. Han DH, Denison MS, Tachibana H, Yamada K: Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Biosci Biotechnol Biochem. 2002 Jul;66(7):1479-87. [12224631 ]
  4. Dang Z: Comparison of relative binding affinities to fish and mammalian estrogen receptors: the regulatory implications. Toxicol Lett. 2010 Feb 15;192(3):298-315. doi: 10.1016/j.toxlet.2009.11.004. Epub 2009 Nov 12. [19913605 ]
  5. 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:
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.64 uMNVS_NR_hARNovascreen
References
  1. Paris F, Balaguer P, Terouanne B, Servant N, Lacoste C, Cravedi JP, Nicolas JC, Sultan C: Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines. Mol Cell Endocrinol. 2002 Jul 31;193(1-2):43-9. [12161000 ]
  2. 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:
Androgen binding
Specific Function:
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.
Gene Name:
SHBG
Uniprot ID:
P04278
Molecular Weight:
43778.755 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation2.138 uMNot AvailableBindingDB 50423506
References
  1. Cherkasov A, Ban F, Santos-Filho O, Thorsteinson N, Fallahi M, Hammond GL: An updated steroid benchmark set and its application in the discovery of novel nanomolar ligands of sex hormone-binding globulin. J Med Chem. 2008 Apr 10;51(7):2047-56. doi: 10.1021/jm7011485. Epub 2008 Mar 11. [18330978 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.31 uMATG_PXR_TRANSAttagene
AC504.38 uMATG_PXRE_CISAttagene
References
  1. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.74 uMNVS_NR_hGRNovascreen
References
  1. 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:
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRG
Uniprot ID:
P62508
Molecular Weight:
51305.485 Da
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