T3DB: 4-Phenylphenol

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (8)XML

Targets (8)

Record Information

Version

2.0

Creation Date

2014-08-12 17:52:05 UTC

Update Date

2014-12-24 20:26:34 UTC

Accession Number

T3D3949

Identification

Common Name

4-Phenylphenol

Class

Small Molecule

Description

4-phenylphenol is estrogen recepto(ER) alpha agonists, antagonists for androgen receptor (AR). It is a weak inhibitors on expression under control of the progesterone receptor(PR).

Compound Type

Industrial/Workplace Toxin
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Synonym
4-Biphenylol
4-Diphenylol
4-Hydroxybiphenyl
4-Hydroxydiphenyl
P-Biphenylol
P-Hydroxybiphenyl
P-Hydroxydiphenyl
P-Phenylphenol
Para-hydroxydiphenyl
Para-phenylphenol

Chemical Formula

C₁₂H₁₀O

Average Molecular Mass

170.207 g/mol

Monoisotopic Mass

170.073 g/mol

CAS Registry Number

92-69-3

IUPAC Name

4-phenylphenol

Traditional Name

phenylphenol

SMILES

OC1=CC=C(C=C1)C1=CC=CC=C1

InChI Identifier

InChI=1S/C12H10O/c13-12-8-6-11(7-9-12)10-4-2-1-3-5-10/h1-9,13H

InChI Key

InChIKey=YXVFYQXJAXKLAK-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Biphenyls and derivatives

Direct Parent

Biphenyls and derivatives

Alternative Parents

Substituents

Biphenyl
1-hydroxy-2-unsubstituted benzenoid
Phenol
Organic oxygen compound
Hydrocarbon derivative
Organooxygen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

hydroxybiphenyls (CHEBI:34422 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	164-166 °C(lit.)
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.28 g/L	ALOGPS
logP	3.24	ALOGPS
logP	3.32	ChemAxon
logS	-2.8	ALOGPS
pKa (Strongest Acidic)	9.89	ChemAxon
pKa (Strongest Basic)	-5.5	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	20.23 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	53.18 m³·mol⁻¹	ChemAxon
Polarizability	18.97 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	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 GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00di-0900000000-0d0e0ba41aa382a5287e	2018-04-09	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0900000000-28d94db1734ec83b3ebf	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00di-0900000000-6d135e0fe1c018c4e323	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0f76-3900000000-be52a1881bb43ba2cb5a	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-0900000000-239b22df9f1af5fbbaa5	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-014i-0900000000-e5403f3402c29a03775c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014i-1900000000-69bd7b5051ebf9466f2b	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00di-4900000000-3b5d174cfebe5bf1a71a	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 90 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 25.16 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

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

Not Available

Symptoms

Not Available

Treatment

Not Available

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

34422

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D3949.pdf

General 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 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	2.08 uM	NVS_NR_hAR	Novascreen

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 ]
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. 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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	8.31 uM	ACEA_T47D_80hr_Positive	ACEA Biosciences
AC50	2.68 uM	ATG_ERa_TRANS	Attagene
AC50	3.05 uM	ATG_ERE_CIS	Attagene
AC50	7.49 uM	Tox21_ERa_LUC_BG1_Agonist	Tox21/NCGC

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 ]
Olsen CM, Meussen-Elholm ET, Samuelsen M, Holme JA, Hongslo JK: Effects of the environmental oestrogens bisphenol A, tetrachlorobisphenol A, tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4'-dihydroxybiphenyl on oestrogen receptor binding, cell proliferation and regulation of oestrogen sensitive proteins in the human breast cancer cell line MCF-7. Pharmacol Toxicol. 2003 Apr;92(4):180-8. [12753421 ]
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

3. 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 ]

Target Details

4. Stromelysin-1

General Function:: Zinc ion binding
Specific Function:: Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
Gene Name:: MMP3
Uniprot ID:: P08254
Molecular Weight:: 53976.84 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Dissociation	280 uM	Not Available	BindingDB 50149238

References

Erlanson DA, McDowell RS, O'Brien T: Fragment-based drug discovery. J Med Chem. 2004 Jul 1;47(14):3463-82. [15214773 ]

Target Details

5. Tyrosine-protein phosphatase non-receptor type 1

General Function:: Zinc ion binding
Specific Function:: Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.
Gene Name:: PTPN1
Uniprot ID:: P18031
Molecular Weight:: 49966.44 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	6165950.019 uM	Not Available	BindingDB 50149238

References

Cross KP, Myatt G, Yang C, Fligner MA, Verducci JS, Blower PE Jr: Finding discriminating structural features by reassembling common building blocks. J Med Chem. 2003 Oct 23;46(22):4770-5. [14561096 ]

Target Details

6. Vascular endothelial growth factor A

General Function:: Vascular endothelial growth factor receptor binding
Specific Function:: Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.
Gene Name:: VEGFA
Uniprot ID:: P15692
Molecular Weight:: 27042.205 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Dissociation	>5000 uM	Not Available	BindingDB 50149238

References

Hajduk PJ, Bures M, Praestgaard J, Fesik SW: Privileged molecules for protein binding identified from NMR-based screening. J Med Chem. 2000 Sep 7;43(18):3443-7. [10978192 ]

Target Details

7. Estrogen receptor beta

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

Type	Value	Assay Type	Assay Source
AC50	8.72 uM	OT_ER_ERaERb_0480	Odyssey Thera
AC50	9.46 uM	OT_ER_ERbERb_1440	Odyssey Thera

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

8. Translocator protein

General Function:: Cholesterol binding
Specific Function:: Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:: TSPO
Uniprot ID:: P30536
Molecular Weight:: 18827.81 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	9.55 uM	NVS_MP_hPBR	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 ]

4-Phenylphenol (T3D3949)

Structure for T3D3949: 4-Phenylphenol

Targets

Binding/Activity Constants

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