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Record Information
Version1.0
Created at2009-01-29 12:50:38 UTC
Updated at2021-06-30 02:06:18 UTC
NP-MRD IDNP0000222
Secondary Accession NumbersNone
Natural Product 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
Thumb
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 Mass207.2291 Da
Monoisotopic Mass207.10078 Da
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=CC=CN=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
Spectra
Spectrum TypeDescriptionDepositor IDDeposition DateView
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Wishart Lab2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, simulated)Varshavi.d262021-08-10View Spectrum
Species
Species of Origin
Species NameSourceReference
Anas platyrhynchos
Anatidae
Anser anser
Bison bison
Bos taurus
Bos taurus X Bison bison
Bubalus bubalis
Capra aegagrus hircus
Cervidae
Cervus canadensis
Columba
Columbidae
Dromaius novaehollandiae
Equus caballus
Gallus gallus
Lagopus muta
Leporidae
Lepus timidus
Melanitta fusca
Meleagris gallopavo
Numida meleagris
Odocoileus
Oryctolagus
Ovis aries
Phasianidae
Phasianus colchicus
Struthio camelus
Sus scrofa
Sus scrofa domestica
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
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point64 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.09 g/LALOGPS
logP0.33ALOGPS
logP0.58ChemAxon
logS-2.3ALOGPS
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
HMDB IDHMDB0011603
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB 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
Good Scents IDNot Available
References
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 ]
  3. Zhang L, Qu Z, Song A, Yang J, Yu J, Zhang W, Zhuang C: Garlic oil blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis by inducing phase II drug-metabolizing enzymes. Food Chem Toxicol. 2021 Sep 23;157:112581. doi: 10.1016/j.fct.2021.112581. [PubMed:34562529 ]
  4. Jin SW, Im JS, Park JH, Kim HG, Lee GH, Kim SJ, Kwack SJ, Kim KB, Chung KH, Lee BM, Kacew S, Jeong HG, Kim HS: Effects of tobacco compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the expression of epigenetically regulated genes in lung carcinogenesis. J Toxicol Environ Health A. 2021 Aug 29:1-16. doi: 10.1080/15287394.2021.1965059. [PubMed:34459362 ]
  5. Hu SC, Min S, Kang HK, Yang DJ, Lewis SM, Davis KJ, Patton RE, Bryant MS, Sepehr E, Trbojevich R, Pearce MG, Bishop ME, Heflich RH, Maisha MP, Felton R, Chemerynski S, Yee SB, Coraggio M, Rosenfeldt H, Yeager RP, Howard PC, Tang Y: 14-Day Nose-Only Inhalation Toxicity and Haber's Rule Study of NNK in Sprague-Dawley Rats. Toxicol Sci. 2021 Sep 28;183(2):319-337. doi: 10.1093/toxsci/kfab094. [PubMed:34329464 ]