T3DB: Phenanthrene

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2009-03-06 18:58:21 UTC

Update Date

2014-12-24 20:21:24 UTC

Accession Number

T3D0246

Identification

Common Name

Phenanthrene

Class

Small Molecule

Description

Phenanthrene is one of over 100 different polycyclic aromatic hydrocarbons (PAHs). PAHs are chemicals that are formed during the incomplete burning of organic substances, such as fossil fuels. They are usually found as a mixture containing two or more of these compounds. (4)

Compound Type

Aromatic Hydrocarbon
Food Toxin
Industrial By-product/Pollutant
Industrial/Workplace Toxin
Natural Compound
Organic Compound
Pollutant
Polycyclic Aromatic Hydrocarbon

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
9,10-Dehydrophenanthrene
Phenanthracene
Phenanthrin
Phenantrin
Ravatite

Chemical Formula

C₁₄H₁₀

Average Molecular Mass

178.229 g/mol

Monoisotopic Mass

178.078 g/mol

CAS Registry Number

85-01-8

IUPAC Name

phenanthrene

Traditional Name

phenanthrene

SMILES

C1=CC=C2C(C=CC3=CC=CC=C23)=C1

InChI Identifier

InChI=1S/C14H10/c1-3-7-13-11(5-1)9-10-12-6-2-4-8-14(12)13/h1-10H

InChI Key

InChIKey=YNPNZTXNASCQKK-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Phenanthrenes and derivatives

Sub Class

Not Available

Direct Parent

Phenanthrenes and derivatives

Alternative Parents

Substituents

Phenanthrene
Naphthalene
Aromatic hydrocarbon
Polycyclic hydrocarbon
Unsaturated hydrocarbon
Hydrocarbon
Aromatic homopolycyclic compound

Molecular Framework

Aromatic homopolycyclic compounds

External Descriptors

phenanthrenes (CHEBI:28851 )
ortho-fused polycyclic arene (CHEBI:28851 )
ortho-fused tricyclic hydrocarbon (CHEBI:28851 )
a ring (PHENANTHRENE-RING )

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

environmental contaminant

Physical Properties

State

Solid

Appearance

Colorless solid.

Experimental Properties

Property	Value
Melting Point	99.2°C
Boiling Point	Not Available
Solubility	0.00115 mg/mL at 25 °C [SCHWARZ,FP (1977)]
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00034 g/L	ALOGPS
logP	4.55	ALOGPS
logP	3.95	ChemAxon
logS	-5.7	ALOGPS
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	0	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	0 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	58.96 m³·mol⁻¹	ChemAxon
Polarizability	20.43 Å³	ChemAxon
Number of Rings	3	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	splash10-004i-0900000000-73152ac8902a46a51b0e	2021-09-24	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0900000000-9b7fcb41bcf755cbca82	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-004i-0900000000-e07754c44a96c14bf7b0	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0fb9-0900000000-fcb3480d5ef5e6c5c5c9	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0900000000-309955037ba0840b44e2	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0900000000-309955037ba0840b44e2	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-0900000000-de91208ace0944a1f046	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-004i-3900000000-2c8c905707eff1036da1	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 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

Oral (4) ; inhalation (4)

Mechanism of Toxicity

The ability of PAH's to bind to blood proteins such as albumin allows them to be transported throughout the body. Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. (4, 5, 2, 3)

Metabolism

PAH metabolism occurs in all tissues, usually by cytochrome P-450 and its associated enzymes. PAHs are metabolized into reactive intermediates, which include epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations. The phenols, quinones, and dihydrodiols can all be conjugated to glucuronides and sulfate esters; the quinones also form glutathione conjugates. (4)

Toxicity Values

LD50: 700 mg/kg (Oral, Mouse) (7) LD50: 700 mg/kg (Intraperitoneal, Mouse) (7) LD50: 56 mg/kg (Intravenous, Mouse) (7)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

3, not classifiable as to its carcinogenicity to humans. (6)

Uses/Sources

PAHs are released into the environment via the combustion of fossil fuels, coke oven emissions and vehicle exhausts, as well as naturally from forest fires and volcanic eruptions. PAHs from these sources may contaminate nearly water systems. They are also found in coal tar and charbroiled food. (4)

Minimum Risk Level

Not Available

Health Effects

PAHs are carcinogens and have been associated with the increased risk of skin, respiratory tract, bladder, stomach, and kidney cancers. They may also cause reproductive effects and depress the immune system. (4)

Symptoms

Acute exposure to PAHs causes irritation and inflammation of the skin and lung tissue. (1)

Treatment

There is no known antidote for PAHs. Exposure is usually handled with symptomatic treatment. (4)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB08381

HMDB ID

Not Available

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

BioCyc ID

CTD ID

Stitch ID

PDB ID

Not Available

ACToR ID

6508

Wikipedia Link

Phenanthrene

References

Synthesis Reference

Kurt Handrick, Georg Kolling, Fritz Mensch, “Anthracene production from phenanthrene.” U.S. Patent US4384152, issued July, 1953.

MSDS

T3D0246.pdf

General References

Santodonato J, Howard P, Basu D: Health and ecological assessment of polynuclear aromatic hydrocarbons. J Environ Pathol Toxicol. 1981 Sep;5(1):1-364. [7310260 ]
Uno S, Dragin N, Miller ML, Dalton TP, Gonzalez FJ, Nebert DW: Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008 Feb 15;44(4):570-83. Epub 2007 Nov 12. [17997381 ]
Padros J, Pelletier E: In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish. Mar Environ Res. 2000 Jul-Dec;50(1-5):347-51. [11460716 ]
ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for PAHs. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Wikipedia. Benzopyrene. Last Updated 22 January 2009. [Link]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
The Physical and Theoretical Chemistry Laboratory of Oxford University (2004). Material Safety Data Sheet (MSDS) for phenanthrene. [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. Aryl hydrocarbon receptor

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

Uno S, Dragin N, Miller ML, Dalton TP, Gonzalez FJ, Nebert DW: Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008 Feb 15;44(4):570-83. Epub 2007 Nov 12. [17997381 ]
Padros J, Pelletier E: In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish. Mar Environ Res. 2000 Jul-Dec;50(1-5):347-51. [11460716 ]
ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for PAHs. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Wikipedia. Benzopyrene. Last Updated 22 January 2009. [Link]

2. DNA

General Function:: Used for biological information storage.
Specific Function:: DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:: 2.15 x 10¹² Da

References

Uno S, Dragin N, Miller ML, Dalton TP, Gonzalez FJ, Nebert DW: Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008 Feb 15;44(4):570-83. Epub 2007 Nov 12. [17997381 ]
Padros J, Pelletier E: In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish. Mar Environ Res. 2000 Jul-Dec;50(1-5):347-51. [11460716 ]
ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for PAHs. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Wikipedia. Benzopyrene. Last Updated 22 January 2009. [Link]

Target Details

3. Glycine N-methyltransferase

General Function:: Glycine n-methyltransferase activity
Specific Function:: Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
Gene Name:: GNMT
Uniprot ID:: Q14749
Molecular Weight:: 32742.0 Da

References

Uno S, Dragin N, Miller ML, Dalton TP, Gonzalez FJ, Nebert DW: Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008 Feb 15;44(4):570-83. Epub 2007 Nov 12. [17997381 ]
Padros J, Pelletier E: In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish. Mar Environ Res. 2000 Jul-Dec;50(1-5):347-51. [11460716 ]
ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for PAHs. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Wikipedia. Benzopyrene. Last Updated 22 January 2009. [Link]

Target Details

4. Cytochrome P450 1B1

General Function:: Oxygen binding
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, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
Gene Name:: CYP1B1
Uniprot ID:: Q16678
Molecular Weight:: 60845.33 Da

References

Shimada T, Tanaka K, Takenaka S, Foroozesh MK, Murayama N, Yamazaki H, Guengerich FP, Komori M: Reverse type I binding spectra of human cytochrome P450 1B1 induced by flavonoid, stilbene, pyrene, naphthalene, phenanthrene, and biphenyl derivatives that inhibit catalytic activity: a structure-function relationship study. Chem Res Toxicol. 2009 Jul;22(7):1325-33. doi: 10.1021/tx900127s. [19563207 ]

Target Details

5. 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

Schmidt JM, Mercure J, Tremblay GB, Page M, Kalbakji A, Feher M, Dunn-Dufault R, Peter MG, Redden PR: De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor. J Med Chem. 2003 Apr 10;46(8):1408-18. [12672240 ]

Target Details

6. 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

References

Schmidt JM, Mercure J, Tremblay GB, Page M, Kalbakji A, Feher M, Dunn-Dufault R, Peter MG, Redden PR: De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor. J Med Chem. 2003 Apr 10;46(8):1408-18. [12672240 ]

Phenanthrene (T3D0246)

Structure for T3D0246: Phenanthrene

Targets

References

References

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