NNK | CAS#64091-91-4 | procarcinogen

MedKoo Cat#: 558428 | Name: NNK

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

NNK is a procarcinogen, a major tobacco-specific toxicant that inhibits the expression of lysyl oxidase, a tumor suppressor.

Chemical Structure

NNK

CAS#64091-91-4

Theoretical Analysis

MedKoo Cat#: 558428

Name: NNK

CAS#: 64091-91-4

Chemical Formula: C10H13N3O2

Exact Mass: 207.1008

Molecular Weight: 207.23

Elemental Analysis: C, 57.96; H, 6.32; N, 20.28; O, 15.44

Price and Availability

Size	Price	Availability	Quantity
25mg	USD 290.00
100mg	USD 410.00
1g	USD 1,450.00

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Synonym

NNK; Nicotine-derived nitrosamine ketone;

IUPAC/Chemical Name

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

InChi Key

FLAQQSHRLBFIEZ-UHFFFAOYSA-N

InChi Code

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

SMILES Code

O=C(C1=CC=CN=C1)CCCN(C)N=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

NNK simultaneously stimulates Bcl2 phosphorylation exclusively at Ser70 and c-Myc at Thr58 and Ser62 through activation of both ERK1/2 and PKCα.

In vitro activity:

NNK simultaneously stimulates Bcl2 phosphorylation exclusively at Ser(70) and c-Myc at Thr(58) and Ser(62) through activation of both ERK1/2 and PKCalpha, which is required for NNK-induced survival and proliferation of human lung cancer cells. Treatment of cells with staurosporine or PD98059 blocks both Bcl2 and c-Myc phosphorylation and results in suppression of NNK-induced proliferation. Reference: J Biol Chem. 2004 Sep 17;279(38):40209-19. https://pubmed.ncbi.nlm.nih.gov/15210690/

In vivo activity:

This study found that oral intake of yamabudo-fr or DBQ affords significant protection against a tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse model of lung tumorigenesis. Yamabudo juice and DBQ inhibited the mutagenicity of NNK in the Ames test using Salmonella typhimurium TA1535 but not S. typhimurium YG7108, an alkylguanine DNA alkyltransferase-deficient strain (same as TA1535 but Δadast::Kmr, Δogtst::Cmr). Yamabudo juice and DBQ might accelerate the repair of DNA damage caused by NNK and reduce DNA damage to cells. Reference: Chem Res Toxicol. 2018 May 21;31(5):358-370. https://pubmed.ncbi.nlm.nih.gov/34087405/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	144.76
	DMSO	43.8	211.12
	Ethanol	25.0	120.64
	PBS (pH 7.2)	10.0	48.26

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 207.23 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Sun Y, Wang H, Chen H, Zhang S, Li J, Zhang J, Tian J, Zhang Y, Hou H, Hu Q. Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells. Molecules. 2022 Jul 29;27(15):4851. doi: 10.3390/molecules27154851. PMID: 35956805; PMCID: PMC9369970. 2. 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 Sep 17;279(38):40209-19. doi: 10.1074/jbc.M404056200. Epub 2004 Jun 21. PMID: 15210690. 3. Arimoto-Kobayashi S, Sasaki K, Hida R, Miyake N, Fujii N, Saiki Y, Daimaru K, Nakashima H, Kubo T, Kiura K. Chemopreventive effects and anti-tumorigenic mechanisms of 2,6-dimethoxy-1,4-benzoquinone, a constituent of Vitis coignetiae Pulliat (crimson glory vine, known as yamabudo in Japan), toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Food Chem Toxicol. 2021 Aug;154:112319. doi: 10.1016/j.fct.2021.112319. Epub 2021 Jun 1. PMID: 34087405. 4. Carlson ES, Upadhyaya P, Villalta PW, Ma B, Hecht SS. Analysis and Identification of 2'-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol. Chem Res Toxicol. 2018 May 21;31(5):358-370. doi: 10.1021/acs.chemrestox.8b00056. Epub 2018 Apr 19. PMID: 29651838; PMCID: PMC5995121.

In vitro protocol:

In vivo protocol:

1. Arimoto-Kobayashi S, Sasaki K, Hida R, Miyake N, Fujii N, Saiki Y, Daimaru K, Nakashima H, Kubo T, Kiura K. Chemopreventive effects and anti-tumorigenic mechanisms of 2,6-dimethoxy-1,4-benzoquinone, a constituent of Vitis coignetiae Pulliat (crimson glory vine, known as yamabudo in Japan), toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Food Chem Toxicol. 2021 Aug;154:112319. doi: 10.1016/j.fct.2021.112319. Epub 2021 Jun 1. PMID: 34087405. 2. Carlson ES, Upadhyaya P, Villalta PW, Ma B, Hecht SS. Analysis and Identification of 2'-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol. Chem Res Toxicol. 2018 May 21;31(5):358-370. doi: 10.1021/acs.chemrestox.8b00056. Epub 2018 Apr 19. PMID: 29651838; PMCID: PMC5995121.

1: Cheng G, Li J, Zheng M, Zhao Y, Zhou J, Li W. NNK, a tobacco-specific carcinogen, inhibits the expression of lysyl oxidase, a tumor suppressor. Int J Environ Res Public Health. 2014 Dec 23;12(1):64-82. doi: 10.3390/ijerph120100064. PubMed PMID: 25546273; PubMed Central PMCID: PMC4306850. 2: Tong M, Yu R, Deochand C, de la Monte SM. Differential Contributions of Alcohol and the Nicotine-Derived Nitrosamine Ketone (NNK) to Insulin and Insulin-Like Growth Factor Resistance in the Adolescent Rat Brain. Alcohol Alcohol. 2015 Nov;50(6):670-9. doi: 10.1093/alcalc/agv101. Epub 2015 Sep 15. PubMed PMID: 26373814; PubMed Central PMCID: PMC4608623. 3: Wu Q, Nadesalingam J, Moodley S, Bai X, Liu M. XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells. Oncotarget. 2015 Jul 20;6(20):18050-65. PubMed PMID: 25980441; PubMed Central PMCID: PMC4627235. 4: Tong M, Yu R, Silbermann E, Zabala V, Deochand C, de la Monte SM. Differential Contributions of Alcohol and Nicotine-Derived Nitrosamine Ketone (NNK) to White Matter Pathology in the Adolescent Rat Brain. Alcohol Alcohol. 2015 Nov;50(6):680-9. doi: 10.1093/alcalc/agv102. Epub 2015 Sep 15. PubMed PMID: 26373813; PubMed Central PMCID: PMC4608624. 5: Zhang D, Lei J, Ma J, Chen X, Sheng L, Jiang Z, Nan L, Xu Q, Duan W, Wang Z, Li X, Wu Z, Wu E, Ma Q, Huo X. β2-adrenogenic signaling regulates NNK-induced pancreatic cancer progression via upregulation of HIF-1α. Oncotarget. 2016 Apr 5;7(14):17760-72. doi: 10.18632/oncotarget.5677. PubMed PMID: 26497365; PubMed Central PMCID: PMC4951248. 6: Zabala V, Tong M, Yu R, Ramirez T, Yalcin EB, Balbo S, Silbermann E, Deochand C, Nunez K, Hecht S, de la Monte SM. Potential contributions of the tobacco nicotine-derived nitrosamine ketone (NNK) in the pathogenesis of steatohepatitis in a chronic plus binge rat model of alcoholic liver disease. Alcohol Alcohol. 2015 Mar;50(2):118-31. doi: 10.1093/alcalc/agu083. Epub 2015 Jan 24. PubMed PMID: 25618784; PubMed Central PMCID: PMC4327341. 7: Tang W, Kuruvilla SA, Galitovskiy V, Pan ML, Grando SA, Mukherjee J. Targeting histone deacetylase in lung cancer for early diagnosis: (18)F-FAHA PET/CT imaging of NNK-treated A/J mice model. Am J Nucl Med Mol Imaging. 2014 Jun 7;4(4):324-32. eCollection 2014. PubMed PMID: 24982818; PubMed Central PMCID: PMC4074498. 8: Li L, Megaraj V, Wei Y, Ding X. Identification of cytochrome P450 enzymes critical for lung tumorigenesis by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): insights from a novel Cyp2abfgs-null mouse. Carcinogenesis. 2014 Nov;35(11):2584-91. doi: 10.1093/carcin/bgu182. Epub 2014 Aug 30. PubMed PMID: 25173884; PubMed Central PMCID: PMC4216058. 9: Wei B, Blount BC, Xia B, Wang L. Assessing exposure to tobacco-specific carcinogen NNK using its urinary metabolite NNAL measured in US population: 2011-2012. J Expo Sci Environ Epidemiol. 2016 May-Jun;26(3):249-56. doi: 10.1038/jes.2014.88. Epub 2015 Jan 7. PubMed PMID: 25564369; PubMed Central PMCID: PMC4520776. 10: Bodhicharla R, Ryde IT, Prasad GL, Meyer JN. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces mitochondrial and nuclear DNA damage in Caenorhabditis elegans. Environ Mol Mutagen. 2014 Jan;55(1):43-50. doi: 10.1002/em.21815. Epub 2013 Sep 7. PubMed PMID: 24014178. 11: Cao B, Zhang Q, Ji H, Liu J, Lang H, Feng M, Zhang J. Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung. Anal Bioanal Chem. 2014 Jul;406(18):4465-71. doi: 10.1007/s00216-014-7851-3. Epub 2014 May 11. PubMed PMID: 24817362. 12: Naizhen X, Linnoila RI, Kimura S. Co-expression of Achaete-Scute Homologue-1 and Calcitonin Gene-Related Peptide during NNK-Induced Pulmonary Neuroendocrine Hyperplasia and Carcinogenesis in Hamsters. J Cancer. 2016 Oct 23;7(14):2124-2131. eCollection 2016. PubMed PMID: 27877229; PubMed Central PMCID: PMC5118677. 13: Jamal QM, Dhasmana A, Lohani M, Firdaus S, Ansari MY, Sahoo GC, Haque S. Binding Pattern Elucidation of NNK and NNAL Cigarette Smoke Carcinogens with NER Pathway Enzymes: an Onco- Informatics Study. Asian Pac J Cancer Prev. 2015;16(13):5311-7. PubMed PMID: 26225671. 14: Hu CW, Hsu YW, Chen JL, Tam LM, Chao MR. Direct analysis of tobacco-specific nitrosamine NNK and its metabolite NNAL in human urine by LC-MS/MS: evidence of linkage to methylated DNA lesions. Arch Toxicol. 2014 Feb;88(2):291-9. doi: 10.1007/s00204-013-1137-y. Epub 2013 Sep 22. PubMed PMID: 24057573. 15: Mennecier G, Torres LN, Cogliati B, Sanches DS, Mori CM, Latorre AO, Chaible LM, Mackowiak II, Nagamine MK, Da Silva TC, Fukumasu H, Dagli ML. Chronic exposure of lung alveolar epithelial type II cells to tobacco-specific carcinogen NNK results in malignant transformation: a new in vitro lung carcinogenesis model. Mol Carcinog. 2014 May;53(5):392-402. doi: 10.1002/mc.21987. Epub 2012 Nov 30. PubMed PMID: 23203541. 16: Ge GZ, Xu TR, Chen C. Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms. Acta Biochim Biophys Sin (Shanghai). 2015 Jul;47(7):477-87. doi: 10.1093/abbs/gmv041. Epub 2015 Jun 3. Review. PubMed PMID: 26040315. 17: 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 PMID: 24830349; PubMed Central PMCID: PMC4074821. 18: Sun Z, Xiao Z. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) regulates CTL activation and memory programming. Biochem Biophys Res Commun. 2013 Jun 7;435(3):472-6. doi: 10.1016/j.bbrc.2013.05.011. Epub 2013 May 11. PubMed PMID: 23673295; PubMed Central PMCID: PMC3787869. 19: Modesto JL, Hull A, Angstadt AY, Berg A, Gallagher CJ, Lazarus P, Muscat JE. NNK reduction pathway gene polymorphisms and risk of lung cancer. Mol Carcinog. 2015 Jun;54 Suppl 1:E94-E102. doi: 10.1002/mc.22187. Epub 2014 Jun 29. PubMed PMID: 24976539. 20: Carson JL, Brighton LE, Jaspers I. Phenotypic modification of human airway epithelial cells in air-liquid interface culture induced by exposure to the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Ultrastruct Pathol. 2015 Apr;39(2):104-9. doi: 10.3109/01913123.2014.960546. Epub 2014 Oct 2. PubMed PMID: 25275891.