Details of the Drug

General Information of Drug (ID: DM4KXT0)

• Drug Name: BRN-3548355
• Synonyms: NNK (carcinogen); 1-Butanone, 4-(methylnitrosoamino)-1-(3-pyridinyl)-; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; 4-(Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; 4-(N-Nitroso-N-methylamino)-1-(3-pyridyl)-1-butanone; 4-Methylnitrosoamino-1-(3-pyridinyl)-1-butanone; 4-[methyl(nitroso)amino]-1-(pyridin-3-yl)butan-1-one; 64091-91-4; 7S395EDO61; CCRIS 1150; CHEBI:32692; MFCD00274580; N-Methyl-N-nitroso-4-oxo-4-(3-pyridyl)butyl amine; NNK; UNII-7S395EDO61

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 207.23
  Topological Polar Surface Area (xlogp); 0.8
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C10H13N3O2
  IUPAC Name: N-methyl-N-(4-oxo-4-pyridin-3-ylbutyl)nitrous amide
  Canonical SMILES: CN(CCCC(=O)C1=CN=CC=C1)N=O
  InChI: FLAQQSHRLBFIEZ-UHFFFAOYSA-N
  InChIKey: 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
• Cross-matching ID:
  PubChem CID: 47289
  ChEBI ID: CHEBI:32692
  CAS Number: 64091-50-5
  INTEDE ID: DR0011

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
NADPH-dependent carbonyl reductase 1 (CBR1)	DE9JFMC	CBR1_HUMAN	Substrate	[2]
Aldo-keto reductase 1C1 (AKR1C1)	DE7P2FB	AK1C1_HUMAN	Substrate	[2]
Aldo-keto reductase 1C2 (AKR1C2)	DEOY5ZM	AK1C2_HUMAN	Substrate	[2]
Aldo-keto reductase 1C4 (AKR1C4)	DEAJN47	AK1C4_HUMAN	Substrate	[2]

References

• [1] Accumulation and persistence of DNA adducts in respiratory tissue of rats following multiple administrations of the tobacco specific carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res. 1986 Mar;46(3):1280-4.
• [2] Characterization of enzymes participating in carbonyl reduction of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human placenta. Chem Biol Interact. 2001 Jan 30;130-132(1-3):737-48.
• [3] Polycyclic aromatic hydrocarbon quinones and glutathione thioethers as substrates and inhibitors of the human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase. J Biol Chem. 1987 Sep 15;262(26):12448-51.
• [4] Flavonoids as inhibitors of human carbonyl reductase 1. Chem Biol Interact. 2008 Jul 30;174(2):98-108.
• [5] In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016 Oct 25;258:153-8.
• [6] Metabolism of prostaglandins by the nonpregnant human uterus. J Clin Endocrinol Metab. 1983 Apr;56(4):678-85.
• [7] The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo. Drug Metab Rev. 2016 May;48(2):159-82.
• [8] Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
• [9] Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3): the V54L mutation restricting the steroid alternative binding and enhancing the 20alpha-HSD activity. J Steroid Biochem Mol Biol. 2014 May;141:135-43.
• [10] Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35.
• [11] The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7.
• [12] Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):213-22.