FRCD

Common Name	2-Methylnaphthalene(F03394)
2D Structure
Description	2-Methylnaphthalene is one of over 100 different polycyclic aromatic hydrocarbons (PAHs). PAHs are chemicals that are formed during the incomplete burning organic substances, such as fossil fuels. They are usually found as a mixture containing two or more of these compounds. (L10)
FRCD ID	F03394
CAS Number	91-57-6
PubChem CID	7055
Formula	C11H10
IUPAC Name	2-methylnaphthalene
InChI Key	QIMMUPPBPVKWKM-UHFFFAOYSA-N
InChI	InChI=1S/C11H10/c1-9-6-7-10-4-2-3-5-11(10)8-9/h2-8H,1H3
Canonical SMILES	CC1=CC2=CC=CC=C2C=C1
Isomeric SMILES	CC1=CC2=CC=CC=C2C=C1
Synonyms	.beta.-Methylnaphthalene 2-METHYLNAPHTHALENE 91-57-6 Naphthalene, 2-methyl- beta-Methylnaphthalene Naphthalene, beta-methyl- UNII-S8MCX3C16H 2-methyl naphthalene 2-methyl-naphthalene HSDB 5274
Classifies	Pollutant
Update Date	Nov 13, 2018 17:07

Kingdom	Organic compounds
Superclass	Benzenoids
Class	Naphthalenes
Subclass	Not available
Intermediate Tree Nodes	Not available
Direct Parent	Naphthalenes
Alternative Parents	Polycyclic hydrocarbons Unsaturated hydrocarbons
Molecular Framework	Aromatic homopolycyclic compounds
Substituents	Naphthalene - Aromatic hydrocarbon - Polycyclic hydrocarbon - Unsaturated hydrocarbon - Hydrocarbon - Aromatic homopolycyclic compound
Description	This compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.

Property Name	Property Value
Molecular Weight	142.201
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	0
Rotatable Bond Count	0
Complexity	128
Monoisotopic Mass	142.078
Exact Mass	142.078
XLogP	3.9
Formal Charge	0
Heavy Atom Count	11
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9704
Human Intestinal Absorption	HIA+	1.0000
Caco-2 Permeability	Caco2+	0.8466
P-glycoprotein Substrate	Non-substrate	0.6749
P-glycoprotein Inhibitor	Non-inhibitor	0.8994
P-glycoprotein Inhibitor	Non-inhibitor	0.9221
Renal Organic Cation Transporter	Non-inhibitor	0.8256
Distribution
Subcellular localization	Lysosome	0.8258
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.7485
CYP450 2D6 Substrate	Non-substrate	0.8811
CYP450 3A4 Substrate	Non-substrate	0.7344
CYP450 1A2 Inhibitor	Inhibitor	0.7333
CYP450 2C9 Inhibitor	Non-inhibitor	0.9359
CYP450 2D6 Inhibitor	Non-inhibitor	0.9231
CYP450 2C19 Inhibitor	Non-inhibitor	0.9026
CYP450 3A4 Inhibitor	Non-inhibitor	0.8710
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.5448
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9225
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.8881
AMES Toxicity	AMES toxic	0.9108
Carcinogens	Non-carcinogens	0.6897
Fish Toxicity	High FHMT	0.9385
Tetrahymena Pyriformis Toxicity	High TPT	0.9975
Honey Bee Toxicity	High HBT	0.7646
Biodegradation	Not ready biodegradable	0.8795
Acute Oral Toxicity	III	0.7963
Carcinogenicity (Three-class)	Warning	0.4452

Model	Value	Unit
Absorption
Aqueous solubility	-5.8273	LogS
Caco-2 Permeability	1.8758	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	1.9099	LD50, mol/kg
Fish Toxicity	0.6527	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	1.2969	pIGC50, ug/L

Title	Journal	Date	Pubmed ID
Biochemical studies of toxic agents. The metabolic formation of 1- and 2-menaphthylmercapturic acid.	Biochem J	1968 Apr	5660632

Targets

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
Mechanism of Action:: 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.

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 ]

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
Mechanism of Action:: 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.

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 ]

General Function:: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:: CYP1A2
Uniprot ID:: P05177
Molecular Weight:: 58293.76 Da

Korhonen LE, Rahnasto M, Mahonen NJ, Wittekindt C, Poso A, Juvonen RO, Raunio H: Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15. [15916432 ]