Drug Information

Drug (ID: DG01799) and It's Reported Resistant Information

• Name: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
• Synonyms: 64091-91-4; 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; NNK (carcinogen); NNK; 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; 1-Butanone, 4-(methylnitrosoamino)-1-(3-pyridinyl)-; 4-(N-Nitroso-N-methylamino)-1-(3-pyridyl)-1-butanone; UNII-7S395EDO61; N-methyl-N-(4-oxo-4-pyridin-3-ylbutyl)nitrous amide; MFCD00274580; 4-Methylnitrosoamino-1-(3-pyridinyl)-1-butanone; 4-(methylnitrosoamino)-1-(3-pyridinyl)-1-butanone; N-Methyl-N-nitroso-4-oxo-4-(3-pyridyl)butyl amine; 4-(Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; 4-[methyl(nitroso)amino]-1-(pyridin-3-yl)butan-1-one; CHEBI:32692; 7S395EDO61; 4-(Nitrosomethylamino)-1-(3-pyridyl)-1-butanone; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-(butanone); 4-[methyl(nitroso)amino]-1-pyridin-3-ylbutan-1-one; Ketone, 3-pyridyl 3-(N-methyl-N-nitrosamino)propyl; N-methyl-N-(4-oxo-4-(pyridin-3-yl)butyl)nitrous amide; N-Methyl-N-[4-oxo-4-(pyridin-3-yl)butyl]nitrous amide; 4-(N-nitrosomethylamino)-1-(3-pyridyl)butan-1-one; CCRIS 1150; BRN 3548355; HSDB 7771; Ozone/NNK; 4-(Nitrosoamino-N-methyl)-1-(3-pyridyl)-1-butanone; 4-(N-Methyl-N-nitrosoamino)-4-(3-pyridyl)-1-butanone; 64091-50-5; DSSTox_CID_881; N-Nitrosonornicotine ketone; N-Nitrosonornicotine-ketone; DSSTox_GSID_20881; 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone; SCHEMBL454516; 1-Butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-; CHEMBL2311069; DTXSID3020881; Nicotine-derived nitrosamine ketone; BCP32075; ZINC5239470; Tox21_303771; AKOS028109857; NCGC00163358-01; NCGC00357285-01; SY062201; CAS-64091-91-4; HY-126477; FT-0616837; FT-0672061; FT-0672062; A50811; Q6138931; 1-Butanone,4-(methylnitrosoamino)-1-(3-pyridinyl)-; 1-Butanone, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl); 4-(1-Methyl-2-oxohydrazino)-1-(3-pyridinyl)-1-butanone #; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) solution; 4-(Methylnitrosoamino)-1-(3-pyridinyl)-1-butanone, analytical standard; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Pancreatic cancer [ICD-11: 2C10]; [2]
• Formula: 5
• IsoSMILES: CN(CCCC(=O)C1=CN=CC=C1)N=O
• InChI: 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
• InChIKey: FLAQQSHRLBFIEZ-UHFFFAOYSA-N
• PubChem CID: 47289
• VARIDT ID: DR0011

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Autophagy protein 5 (ATG5) [2]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: beta2AR-Akt feedback loop signalling pathway; Regulation; N.A.
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: Colony formation assay; Stem cell sphere formation assay
• Mechanism Description: In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy-related markers autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), and Beclin1. Furthermore, the results showed that NNK-promoted stemness and gemcitabine resistance was partially dependent on the role of NNK in cell autophagy, which is mediated by the beta2-adrenergic receptor (beta2AR)-Akt axis. Finally, we proved that NNK intervention could not only activate beta2AR, but also increase its expression, making beta2AR and Akt form a feedback loop. Overall, these findings show that the NNK-induced beta2AR-Akt feedback loop promotes stemness and gemcitabine resistance in pancreatic cancer cells.

Key Molecule: Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) [2]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: beta2AR-Akt feedback loop signalling pathway; Regulation; N.A.
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: Colony formation assay; Stem cell sphere formation assay
• Mechanism Description: In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy-related markers autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), and Beclin1. Furthermore, the results showed that NNK-promoted stemness and gemcitabine resistance was partially dependent on the role of NNK in cell autophagy, which is mediated by the beta2-adrenergic receptor (beta2AR)-Akt axis. Finally, we proved that NNK intervention could not only activate beta2AR, but also increase its expression, making beta2AR and Akt form a feedback loop. Overall, these findings show that the NNK-induced beta2AR-Akt feedback loop promotes stemness and gemcitabine resistance in pancreatic cancer cells.

Key Molecule: Beclin-1 (BECN1) [2]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: beta2AR-Akt feedback loop signalling pathway; Regulation; N.A.
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: Colony formation assay; Stem cell sphere formation assay
• Mechanism Description: In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy-related markers autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), and Beclin1. Furthermore, the results showed that NNK-promoted stemness and gemcitabine resistance was partially dependent on the role of NNK in cell autophagy, which is mediated by the beta2-adrenergic receptor (beta2AR)-Akt axis. Finally, we proved that NNK intervention could not only activate beta2AR, but also increase its expression, making beta2AR and Akt form a feedback loop. Overall, these findings show that the NNK-induced beta2AR-Akt feedback loop promotes stemness and gemcitabine resistance in pancreatic cancer cells.

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: EGFR antisense RNA 1 (EGFR-AS1) [1]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Down-regulation; Interaction
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Notch1 signaling pathway; Activation; hsa04330
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCH-H23 cells; N.A.; N.A.; N.A.
• In Vitro Model: HEK293NT cells; N.A.; N.A.; N.A.
• In Vivo Model: Female nude mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: EGFR-AS1/HIF2A regulates the expression of FOXP3 to impact the cancer stemness of smoking-related non-small cell lung cancer.

References

• Ref 1: EGFR-AS1/HIF2A regulates the expression of FOXP3 to impact the cancer stemness of smoking-related non-small cell lung cancerTher Adv Med Oncol. 2019 Jun 13;11:1758835919855228. doi: 10.1177/1758835919855228. eCollection 2019.
• Ref 2: NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a beta2AR-Akt feedback loop that activates autophagy. Mol Oncol. 2022 Aug;16(15):2881-2895.