nnk

Names

[ Name ]:
nnk

[Synonym ]:
4-[Methyl(nitroso)amino]-1-(3-pyridinyl)-1-butanone
Nicotine-derived nitrosamine ketone
1-Butanone, 4-(methylnitrosoamino)-1-(3-pyridinyl)-
4-(n-nitrosomethylamino)-1-(3-pyridyl)-1-butanone
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
N-Nitrosonornicotine ketone
NNK
Ozone/NNK
MFCD00274580
N-methyl-N-(4-oxo-4-pyridin-3-ylbutyl)nitrous amide
1-Butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-
4-[Methyl(nitroso)amino]-1-(pyridin-3-yl)butan-1-one

Biological Activity

[Description]:

NNK is a nicotine-nitrosated derivative. NNK simultaneously stimulates Bcl2 phosphorylation exclusively at Ser70 and c-Myc at Thr58 and Ser62 through activation of both ERK1/2 and PKCα[1]. NNK induces survival and proliferation of human lung cancer cells. NNK can be used for lung cancer mice model structure[2].

[Related Catalog]:

Research Areas >> Cancer

[Target]

Human Endogenous Metabolite

[In Vitro]

NNK (100 pM; 0-60 min) stimulates activation of PKCα and MAPKs ERK1/2 that directly induce c-Myc phosphorylation[1]. NNK (100 pM; 96 hours) enhances proliferation of cells expressing WT but not AA c-Myc mutant[1]. Western Blot Analysis Cell Line: NCI-H82 cells[1] Concentration: 100 pM Incubation Time: 0-60 min Result: Stimulated activation of PKCα and MAPKs ERK1/2 that directly induced c-Myc phosphorylation. Apoptosis Analysis Cell Line: H1299 lung cancer cells[1] Concentration: 100 pM Incubation Time: 96 hours Result: Enhanced proliferation of cells expressing WT but not T58A/S62A c-Myc mutant.

[References]

[1]. Jin Z, Gao F, Flagg T, Deng X. Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation. J Biol Chem. 2004;279(38):40209-40219.

[2]. Castonguay A, Pepin P, Stoner GD. Lung tumorigenicity of NNK given orally to A/J mice: its application to chemopreventive efficacy studies. Exp Lung Res. 1991;17(2):485-499.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
423.9±25.0 °C at 760 mmHg

[ Melting Point ]:
63-65ºC

[ Molecular Formula ]:
C₁₀H₁₃N₃O₂

[ Molecular Weight ]:
207.229

[ Flash Point ]:
210.2±23.2 °C

[ Exact Mass ]:
207.100784

[ PSA ]:
62.63000

[ LogP ]:
0.09

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.557

[ Storage condition ]:
Amber Vial, -20°C Freezer

[ Stability ]:
Stable. Incompatible with strong oxidizing agents.

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: OB6465000

CHEMICAL NAME :: Ketone, 3-pyridyl 3-(N-methyl-N-nitrosamino)propyl

CAS REGISTRY NUMBER :: 64091-91-4

BEILSTEIN REFERENCE NO. :: 3548355

LAST UPDATED :: 199612

DATA ITEMS CITED :: 52

MOLECULAR FORMULA :: C10-H13-N3-O2

MOLECULAR WEIGHT :: 207.26

WISWESSER LINE NOTATION :: T6NJ CV3N1&NO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2156 mg/kg/61W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 68396 ug/kg/20W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 880 mg/kg/95W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 41452 ug/kg

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 960 mg/kg/95W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 20 mg/kg female 15 day(s) after conception

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Reproductive - Tumorigenic effects - transplacental tumorigenesis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 1504 mg/kg/25W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intratracheal

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 50 ug/kg

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Reproductive - Tumorigenic effects - transplacental tumorigenesis

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 880 mg/kg/7W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 93 mg/kg

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2700 mg/kg/20W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Liver - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 68396 ug/kg/20W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2700 mg/kg/20W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Liver - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 106 mg/kg/20W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 166 mg/kg/7W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 300 mg/kg/3D-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Reproductive - Tumorigenic effects - transplacental tumorigenesis

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 300 mg/kg/3D-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Liver - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 400 mg/kg/16W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intratracheal

DOSE :: 50 mg/kg

SEX/DURATION :: female 15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Tumorigenic effects - transplacental tumorigenesis

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Morphological transformation

TYPE OF TEST :: DNA damage

TYPE OF TEST :: DNA adduct

TYPE OF TEST :: DNA adduct

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

MUTATION DATA

TYPE OF TEST :: Unscheduled DNA synthesis

TEST SYSTEM :: Rodent - rabbit Cells - not otherwise specified

DOSE/DURATION :: 2 mmol/L

REFERENCE :: CBTOE2 Cell Biology and Toxicology. (Princeton Scientific Pub., Inc., 301 N. Harrison St., CN 5279, Princeton, NJ 08540) V.1- 1984- Volume(issue)/page/year: 6,399,1990 *** REVIEWS *** IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 37,209,1985 IARC Cancer Review:Human No Adequate Data IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 37,209,1985 IARC Cancer Review:Group 2B IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H317-H351

[ Precautionary Statements ]:
P280-P301 + P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
R26/27/28;R45

[ Safety Phrases ]:
S45-S53

[ RIDADR ]:
UN 2811

[ RTECS ]:
OB6465000

[ Packaging Group ]:
II

[ Hazard Class ]:
6.1

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent carcinogens for the rat esophagus and lung, respectively. Consistent w...

nnk