NNN | CAS#80508-23-2 | N-nitrosamine carcinogen

MedKoo Cat#: 464714 | Name: NNN

Featured

Description:

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

N’-Nitrosonornicotine (NNN) is a tobacco-specific N-nitrosamine and carcinogen that has been found in unburned tobacco and cigarette smoke. It induces the formation of DNA adducts in isolated rat nasal mucosa and esophagus. N'-Nitrosonornicotine induces tumor formation in rat esophagus and nasal cavity, mouse lung, forestomach, and trachea, and hamster trachea and forebrain. Urinary levels of N'-nitrosonornicotine are positively correlated with the risk of esophageal cancer in smokers.

Chemical Structure

NNN

CAS#80508-23-2

Theoretical Analysis

MedKoo Cat#: 464714

Name: NNN

CAS#: 80508-23-2

Chemical Formula: C9H11N3O

Exact Mass: 177.0902

Molecular Weight: 177.21

Elemental Analysis: C, 61.00; H, 6.26; N, 23.71; O, 9.03

Price and Availability

Size	Price	Availability	Quantity
50mg	USD 350.00	2 Weeks
100mg	USD 550.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

NNN; N'-Nitrosonornicotine; N' Nitrosonornicotine;

IUPAC/Chemical Name

3-(1-nitrosopyrrolidin-2-yl)pyridine

InChi Key

XKABJYQDMJTNGQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C9H11N3O/c13-11-12-6-2-4-9(12)8-3-1-5-10-7-8/h1,3,5,7,9H,2,4,6H2

SMILES Code

O=NN1C(CCC1)C2=CN=CC=C2

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

Stock Solution Storage

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

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

N’-Nitrosonornicotine (NNN) is a tobacco-specific N-nitrosamine and carcinogen.

In vitro activity:

Whole-cell recording in combination with the cell-flow technique for agonist and inhibitor application in the millisecond time region revealed that NNN inhibits the activity of neuronal nAChR expressed in HEK or PC12, whereas weak inhibitory effects on muscle-type nAChR were observed at NNN concentrations up to 3 mM. NNN-induced inhibition of nicotine-evoked α3β4 nAChR activity was dose-dependent with an inhibitory constant (IC(50)) of 0.92 ± 0.05 mM. Reference: J Mol Neurosci. 2013 Jan;49(1):52-61. https://pubmed.ncbi.nlm.nih.gov/22847530/

In vivo activity:

This study shown that (S)-N'-Nitrosonornicotine [(S)-NNN], the major form of NNN in tobacco products, is a potent oral cavity and esophageal carcinogen in rats. To determine the early molecular alterations induced by (S)-NNN in the oral and esophageal mucosa, this study administered the carcinogen to rats in the drinking water for 10 wk and global gene expression alterations were analyzed by RNA sequencing. Interrogation of TCGA data sets showed that genes deregulated by (S)-NNN in rat tissues (Fetub, Ly6e, Nr1d1, Cacna1c, Cd80, and Dgkg) are also altered in esophageal and head and neck tumors. Reference: Mol Carcinog. 2016 Dec;55(12):2168-2182. https://pubmed.ncbi.nlm.nih.gov/26785143/

Preparing Stock Solutions

The following data is based on the product molecular weight 177.21 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. Nunes-Alves A, Nery AA, Ulrich H. Tobacco nitrosamine N-nitrosonornicotine as inhibitor of neuronal nicotinic acetylcholine receptors. J Mol Neurosci. 2013 Jan;49(1):52-61. doi: 10.1007/s12031-012-9859-5. Epub 2012 Jul 31. PMID: 22847530. 2. Mao YA, Zhong KJ, Wei WZ, Wei XL, Lu HB. Inhibition by N'-nitrosonornicotine of the catalytic activity of glutamate dehydrogenase in alpha-ketoglutarate amination. J Enzyme Inhib Med Chem. 2005 Feb;20(1):89-94. doi: 10.1080/14756360410001733702. PMID: 15895690. 3. Khammanivong A, Anandharaj A, Qian X, Song JM, Upadhyaya P, Balbo S, Bandyopadhyay D, Dickerson EB, Hecht SS, Kassie F. Transcriptome profiling in oral cavity and esophagus tissues from (S)-N'-nitrosonornicotine-treated rats reveals candidate genes involved in human oral cavity and esophageal carcinogenesis. Mol Carcinog. 2016 Dec;55(12):2168-2182. doi: 10.1002/mc.22459. Epub 2016 Jan 19. PMID: 26785143; PMCID: PMC5142294. 4. Yang J, Villalta PW, Upadhyaya P, Hecht SS. Analysis of O(6)-[4-(3-Pyridyl)-4-oxobut-1-yl]-2'-deoxyguanosine and Other DNA Adducts in Rats Treated with Enantiomeric or Racemic N'-Nitrosonornicotine. Chem Res Toxicol. 2016 Jan 19;29(1):87-95. doi: 10.1021/acs.chemrestox.5b00425. Epub 2015 Dec 18. PMID: 26633576; PMCID: PMC5168933.

In vitro protocol:

In vivo protocol:

1. Khammanivong A, Anandharaj A, Qian X, Song JM, Upadhyaya P, Balbo S, Bandyopadhyay D, Dickerson EB, Hecht SS, Kassie F. Transcriptome profiling in oral cavity and esophagus tissues from (S)-N'-nitrosonornicotine-treated rats reveals candidate genes involved in human oral cavity and esophageal carcinogenesis. Mol Carcinog. 2016 Dec;55(12):2168-2182. doi: 10.1002/mc.22459. Epub 2016 Jan 19. PMID: 26785143; PMCID: PMC5142294. 2. Yang J, Villalta PW, Upadhyaya P, Hecht SS. Analysis of O(6)-[4-(3-Pyridyl)-4-oxobut-1-yl]-2'-deoxyguanosine and Other DNA Adducts in Rats Treated with Enantiomeric or Racemic N'-Nitrosonornicotine. Chem Res Toxicol. 2016 Jan 19;29(1):87-95. doi: 10.1021/acs.chemrestox.5b00425. Epub 2015 Dec 18. PMID: 26633576; PMCID: PMC5168933.

1: Edwards RL Jr, Venugopal PD, Hsieh JR. Aquatic toxicity of waterpipe wastewater chemicals. Environ Res. 2021 Apr 28;197:111206. doi: 10.1016/j.envres.2021.111206. Epub ahead of print. PMID: 33932480. 2: Bordoloi D, Padmavathi G, Banik K, Devi KA, Harsha C, Girisa S, Buhrmann C, Shakibaei M, Kunnumakkara AB. Human tumor necrosis factor alpha-induced protein eight-like 1 exhibited potent anti-tumor effect through modulation of proliferation, survival, migration and invasion of lung cancer cells. Mol Cell Biochem. 2021 Apr 25. doi: 10.1007/s11010-021-04060-1. Epub ahead of print. PMID: 33895911. 3: Li Y, Carlson ES, Zarth AT, Upadhyaya P, Hecht SS. Investigation of 2'-Deoxyadenosine-Derived Adducts Specifically Formed in Rat Liver and Lung DNA by N'-Nitrosonornicotine Metabolism. Chem Res Toxicol. 2021 Apr 19;34(4):1004-1015. doi: 10.1021/acs.chemrestox.1c00012. Epub 2021 Mar 15. PMID: 33720703. 4: Li Y, Hecht SS. Identification of an N'-Nitrosonornicotine-Specific Deoxyadenosine Adduct in Rat Liver and Lung DNA. Chem Res Toxicol. 2021 Apr 19;34(4):992-1003. doi: 10.1021/acs.chemrestox.1c00013. Epub 2021 Mar 11. PMID: 33705110. 5: Edwards SH, Hassink MD, Taylor KM, Watson CH, Kuklenyik P, Kimbrell B, Wang L, Chen P, Valentín-Blasini L. Tobacco-Specific Nitrosamines in the Tobacco and Mainstream Smoke of Commercial Little Cigars. Chem Res Toxicol. 2021 Apr 19;34(4):1034-1045. doi: 10.1021/acs.chemrestox.0c00367. Epub 2021 Mar 5. PMID: 33667338. 6: Deng H, Wang Y, Wang J, Liu S, Ji Y, Fan Z, Li Z, Yang F, Bian Z, Tang G. Separation of N'-nitrosonornicotine isomers and enantiomers by supercritical fluid chromatography tandem mass spectrometry. J Chromatogr A. 2021 Mar 29;1641:461971. doi: 10.1016/j.chroma.2021.461971. Epub 2021 Feb 8. PMID: 33626439. 7: Eshraghian EA, Al-Delaimy WK. A review of constituents identified in e-cigarette liquids and aerosols. Tob Prev Cessat. 2021 Feb 10;7:10. doi: 10.18332/tpc/131111. PMID: 33585727; PMCID: PMC7873740. 8: Najme R, Zhuang S, Qiu J, Lu Z. Identification and characterization of Nornicotine degrading strain Arthrobacter sp. NOR5. Sci Total Environ. 2021 Apr 10;764:142894. doi: 10.1016/j.scitotenv.2020.142894. Epub 2020 Oct 14. PMID: 33131868. 9: Jaccard G, Tafin Djoko D, Korneliou A, Belushkin M. Analysis of waterpipe aerosol constituents in accordance with the ISO standard 22486. Toxicol Rep. 2020 Oct 12;7:1344-1349. doi: 10.1016/j.toxrep.2020.10.007. PMID: 33102137; PMCID: PMC7569180. 10: Guo J, Chen H, Upadhyaya P, Zhao Y, Turesky RJ, Hecht SS. Mass Spectrometric Quantitation of Apurinic/Apyrimidinic Sites in Tissue DNA of Rats Exposed to Tobacco-Specific Nitrosamines and in Lung and Leukocyte DNA of Cigarette Smokers and Nonsmokers. Chem Res Toxicol. 2020 Sep 21;33(9):2475-2486. doi: 10.1021/acs.chemrestox.0c00265. Epub 2020 Sep 9. PMID: 32833447; PMCID: PMC7574376. 11: Xia B, Blount BC, Guillot T, Brosius C, Li Y, Van Bemmel DM, Kimmel HL, Chang CM, Borek N, Edwards KC, Lawrence C, Hyland A, Goniewicz ML, Pine BN, Xia Y, Bernert JT, De Castro BR, Lee J, Brown JL, Arnstein S, Choi D, Wade EL, Hatsukami D, Ervies G, Cobos A, Nicodemus K, Freeman D, Hecht SS, Conway K, Wang L. Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014). Nicotine Tob Res. 2021 Feb 16;23(3):573-583. doi: 10.1093/ntr/ntaa110. PMID: 32716026; PMCID: PMC7885786. 12: Kankanamage RNT, Ghosh AB, Jiang D, Gkika K, Keyes T, Achola LA, Suib S, Rusling JF. Metabolites of Tobacco- and E-Cigarette-Related Nitrosamines Can Drive Cu2+-Mediated DNA Oxidation. Chem Res Toxicol. 2020 Aug 17;33(8):2072-2086. doi: 10.1021/acs.chemrestox.0c00027. Epub 2020 Aug 4. PMID: 32672941; PMCID: PMC7510339. 13: Nasrin S, Chen G, Watson CJW, Lazarus P. Comparison of tobacco-specific nitrosamine levels in smokeless tobacco products: High levels in products from Bangladesh. PLoS One. 2020 May 26;15(5):e0233111. doi: 10.1371/journal.pone.0233111. PMID: 32453764; PMCID: PMC7250445. 14: Wu J, Wang Y. Replication of Pyridyloxobutyl Phosphotriester Lesions in Cells. Chem Res Toxicol. 2020 Feb 17;33(2):308-311. doi: 10.1021/acs.chemrestox.9b00485. Epub 2020 Jan 14. PMID: 31916443; PMCID: PMC7032042. 15: Song Z, Sui X, Li M, Gao Y, Li W, Zhao L, Li F, Yao X, Liu C, Wang B. Development of a nornicotine-reduced flue-cured tobacco line via EMS mutagenesis of nicotine N-demethylase genes. Plant Signal Behav. 2020;15(2):1710053. doi: 10.1080/15592324.2019.1710053. Epub 2020 Jan 3. PMID: 31900036; PMCID: PMC7053972. 16: Kubica P. Ultrasound-Assisted Solvent Extraction of a Porous Membrane Packed Sample for the Determination of Tobacco-Specific Nitrosamines in the Replacement Liquids for E-Cigarettes. Molecules. 2019 Dec 17;24(24):4618. doi: 10.3390/molecules24244618. PMID: 31861109; PMCID: PMC6943691. 17: Belushkin M, Tafin Djoko D, Esposito M, Korneliou A, Jeannet C, Lazzerini M, Jaccard G. Selected Harmful and Potentially Harmful Constituents Levels in Commercial e-Cigarettes. Chem Res Toxicol. 2020 Feb 17;33(2):657-668. doi: 10.1021/acs.chemrestox.9b00470. Epub 2019 Dec 31. Erratum in: Chem Res Toxicol. 2020 Sep 21;33(9):2487. PMID: 31859484. 18: Bordoloi D, Banik K, Padmavathi G, Vikkurthi R, Harsha C, Roy NK, Singh AK, Monisha J, Wang H, Kumar AP, Kunnumakkara AB. TIPE2 Induced the Proliferation, Survival, and Migration of Lung Cancer Cells Through Modulation of Akt/mTOR/NF- κB Signaling Cascade. Biomolecules. 2019 Dec 6;9(12):836. doi: 10.3390/biom9120836. PMID: 31817720; PMCID: PMC6995575. 19: Suzuki S, Cohen SM, Arnold LL, Pennington KL, Kato H, Naiki T, Naiki-Ito A, Yamashita Y, Takahashi S. Cotinine, a major nicotine metabolite, induces cell proliferation on urothelium in vitro and in vivo. Toxicology. 2020 Jan 15;429:152325. doi: 10.1016/j.tox.2019.152325. Epub 2019 Nov 1. PMID: 31678612. 20: Neves Cruz J, Santana de Oliveira M, Gomes Silva S, Pedro da Silva Souza Filho A, Santiago Pereira D, Lima E Lima AH, de Aguiar Andrade EH. Insight into the Interaction Mechanism of Nicotine, NNK, and NNN with Cytochrome P450 2A13 Based on Molecular Dynamics Simulation. J Chem Inf Model. 2020 Feb 24;60(2):766-776. doi: 10.1021/acs.jcim.9b00741. Epub 2019 Oct 28. PMID: 31622091.