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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2009-01-29 12:50:38 UTC
Update Date2021-09-07 17:05:27 UTC
HMDB IDHMDB0011603
Secondary Accession Numbers
  • HMDB11603
Metabolite Identification
Common Name4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
Description4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (also known as NNK) is a potent tobacco-specific nitrosamine derived from nicotine. It plays a key role in human tobacco-related cancers (PMID:24830349 ). NNK is found in cured tobacco and is also produced during its burning or combustion in cigarettes. NNK is abundantly present in cigarette smoke (20-280 ng/cigarette). Electronic cigarettes (e-cigarettes) do not convert nicotine to NNK due to their lower operating temperatures. NNK is a procarcinogen. This means it must be activated by cytochrome P450 enzymes (CYP2A6 and CYP2B6) to become a carcinogen (PMID:24830349 ). NNK can also be activated by myeloperoxidase (MPO) and epoxide hydrolase (EPHX1). All activation processes lead to the formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol from NNK, which is called NNAL (PMID:24830349 ). NNAL can be detoxified via glucuronidation via glucuronidases. Once NNK is activated to NNAL, this compound initiates a cascade of signalling pathways (for example ERK1/2, NFκB, PI3K/Akt, MAPK, FasL, K-ras), resulting in uncontrolled cellular proliferation and tumorigenesis. NNK is known as a mutagen and can cause point mutations that affect cell growth proliferation and differentiation. NNK also targets the SULT1A1, TGF-beta, and angiotensin II genes. NNK plays a key role in gene silencing, gene modification, and carcinogenesis. NNK has been implicated in tumour promotion by activating nicotinic acetylcholine receptors (nAChRs) and β-adrenergic receptors (β-AdrRs), leading to downstream activation of parallel signal transduction pathways that facilitate tumour progression (PMID:24830349 ). Antioxidants such as EGCG (from green tea) inhibit lung tumorigenesis by NNK.
Structure
Data?1582752928
Synonyms
ValueSource
4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneChEBI
NNKChEBI
NNK (Carcinogen)ChEBI
4-(Methylnitrosoamino)-1-(3-pyridyl)-1-butanoneHMDB
4'-(Nitrosomethylamino)-1-(3-pyridyl)-1-butanoneHMDB
NNK CPDHMDB
4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanoneHMDB
4-(Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneHMDB
4-(Methylintrosamino)-1-(3-pyridyl)-1-butanoneHMDB
4-(Methylnitrosoamino)-1-(3-pyridinyl)-1-butanoneHMDB
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanoneChEBI
Chemical FormulaC10H13N3O2
Average Molecular Weight207.2291
Monoisotopic Molecular Weight207.100776675
IUPAC Name4-[methyl(nitroso)amino]-1-(pyridin-3-yl)butan-1-one
Traditional Namennk (carcinogen)
CAS Registry Number64091-91-4
SMILES
CN(CCCC(=O)C1=CN=CC=C1)N=O
InChI Identifier
InChI=1S/C10H13N3O2/c1-13(12-15)7-3-5-10(14)9-4-2-6-11-8-9/h2,4,6,8H,3,5,7H2,1H3
InChI KeyFLAQQSHRLBFIEZ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as aryl alkyl ketones. These are ketones have the generic structure RC(=O)R', where R = aryl group and R'=alkyl group.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentAryl alkyl ketones
Alternative Parents
Substituents
  • Aryl alkyl ketone
  • Pyridine
  • Heteroaromatic compound
  • Organic n-nitroso compound
  • Organic nitroso compound
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Source

Route of exposure

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point64 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Spectral PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility1.09 g/LALOGPS
logP10(0.33) g/LALOGPS
logP10(0.58) g/LChemAxon
logS10(-2.3) g/LALOGPS
pKa (Strongest Acidic)15.47ChemAxon
pKa (Strongest Basic)3.96ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area62.63 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity57.25 m³·mol⁻¹ChemAxon
Polarizability21.12 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+148.94731661259
DarkChem[M-H]-144.43331661259

Predicted Kovats Retention Indices

Not Available
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ab9-9800000000-57c49f29c9d7332bea222017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 10V, Positive-QTOFsplash10-0a4i-1980000000-6eed182d10c9a03751b72016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 20V, Positive-QTOFsplash10-0002-3910000000-5fed6b71985ed1afcab42016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 40V, Positive-QTOFsplash10-001m-9600000000-1c5f7245d666beff11f22016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 10V, Negative-QTOFsplash10-0a4i-3390000000-e76106f4b8f69d27d9aa2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 20V, Negative-QTOFsplash10-0a70-9840000000-3d022ffc7f1a61b3d6d02016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 40V, Negative-QTOFsplash10-056r-9100000000-1782fbf95a7044f769a62016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 10V, Positive-QTOFsplash10-0002-0920000000-1d8ea81c64d584ea02d12021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 20V, Positive-QTOFsplash10-0002-1900000000-63e35eaa2366ca02b75d2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 40V, Positive-QTOFsplash10-001i-7900000000-5f96473ea00e041d2dcc2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 10V, Negative-QTOFsplash10-0a4i-0090000000-482b470c4a0ac6884d932021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 20V, Negative-QTOFsplash10-0a6r-9820000000-35e475a0c732f383cc122021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone 40V, Negative-QTOFsplash10-00or-9300000000-37d4b4467865dbb44ac72021-09-24Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Experimental 1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)2021-10-10Wishart LabView Spectrum
Experimental 2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)2012-12-05Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB028314
KNApSAcK IDNot Available
Chemspider ID43038
KEGG Compound IDC16453
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNNK
METLIN IDNot Available
PubChem Compound47289
PDB IDNot Available
ChEBI ID32692
Food Biomarker OntologyNot Available
VMH IDM00932
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Smith TJ, Guo Z, Guengerich FP, Yang CS: Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P450 1A2 and its inhibition by phenethyl isothiocyanate. Carcinogenesis. 1996 Apr;17(4):809-13. [PubMed:8625495 ]
  2. Xue J, Yang S, Seng S: Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN. Cancers (Basel). 2014 May 14;6(2):1138-56. doi: 10.3390/cancers6021138. [PubMed:24830349 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.
Gene Name:
CBR1
Uniprot ID:
P16152
Molecular weight:
30374.73
Reactions
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone + NADPH + Hydrogen Ion → 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol + NADPdetails
General function:
Involved in oxidoreductase activity
Specific function:
Has low NADPH-dependent oxidoreductase activity towards 4-benzoylpyridine and menadione (in vitro).
Gene Name:
CBR3
Uniprot ID:
O75828
Molecular weight:
30849.97
Reactions
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone + NADPH + Hydrogen Ion → 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol + NADPdetails
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).
Gene Name:
HSD11B1
Uniprot ID:
P28845
Molecular weight:
32400.665
Reactions
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone + NADPH + Hydrogen Ion → 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol + NADPdetails