Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVUDLT3)

• DOT Name: Cytochrome P450 2A13 (CYP2A13)
• Synonyms: EC 1.14.14.1; CYPIIA13
• Gene Name: CYP2A13
• UniProt ID: CP2AD_HUMAN
• PDB ID: 2P85; 2PG5; 2PG6; 2PG7; 3T3S; 4EJG; 4EJH; 4EJI
• EC Number: 1.14.14.1
• Pfam ID: PF00067
• Sequence:
  MLASGLLLVTLLACLTVMVLMSVWRQRKSRGKLPPGPTPLPFIGNYLQLNTEQMYNSLMK
  ISERYGPVFTIHLGPRRVVVLCGHDAVKEALVDQAEEFSGRGEQATFDWLFKGYGVAFSN
  GERAKQLRRFSIATLRGFGVGKRGIEERIQEEAGFLIDALRGTHGANIDPTFFLSRTVSN
  VISSIVFGDRFDYEDKEFLSLLRMMLGSFQFTATSTGQLYEMFSSVMKHLPGPQQQAFKE
  LQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFF
  AGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYTEAVIHEIQ
  RFGDMLPMGLAHRVNKDTKFRDFFLPKGTEVFPMLGSVLRDPRFFSNPRDFNPQHFLDKK
  GQFKKSDAFVPFSIGKRYCFGEGLARMELFLFFTTIMQNFRFKSPQSPKDIDVSPKHVGF
  ATIPRNYTMSFLPR
• Function: Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.
• Tissue Specificity: Expressed in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle.
• KEGG Pathway:
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Chemical carcinogenesis - D. adducts (hsa05204)
• Reactome Pathway:
  Xenobiotics (R-HSA-211981)
  CYP2E1 reactions (R-HSA-211999)
  Aflatoxin activation and detoxification (R-HSA-5423646)
  Fatty acids (R-HSA-211935)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Amodiaquine	DME4RA8	Approved	Cytochrome P450 2A13 (CYP2A13) increases the metabolism of Amodiaquine.	[4]
9-phenanthrol	DMJFBQ1	Investigative	Cytochrome P450 2A13 (CYP2A13) increases the abundance of 9-phenanthrol.	[8]

This DOT Affected the Biotransformations of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
HELENALIN	DMMCI4H	Terminated	Cytochrome P450 2A13 (CYP2A13) increases the oxidation of HELENALIN.	[5]
Coumarin	DM0N8ZM	Investigative	Cytochrome P450 2A13 (CYP2A13) decreases the hydroxylation of Coumarin.	[6]
BRN-3548355	DM4KXT0	Investigative	Cytochrome P450 2A13 (CYP2A13) decreases the hydroxylation of BRN-3548355.	[6]
Chrysin	DM7V2LG	Investigative	Cytochrome P450 2A13 (CYP2A13) increases the oxidation of Chrysin.	[7]
NSC-26745	DMNX245	Investigative	Cytochrome P450 2A13 (CYP2A13) increases the oxidation of NSC-26745.	[7]
Acenaphthenol	DMT3QYZ	Investigative	Cytochrome P450 2A13 (CYP2A13) increases the oxidation of Acenaphthenol.	[9]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytochrome P450 2A13 (CYP2A13).	[1]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Cytochrome P450 2A13 (CYP2A13).	[2]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Cytochrome P450 2A13 (CYP2A13).	[2]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytochrome P450 2A13 (CYP2A13).	[3]

References

• [1] CYP1A1/1B1 and CYP2A6/2A13 activity is conserved in cultures of differentiated primary human tracheobronchial epithelial cells. Toxicol In Vitro. 2011 Jun;25(4):922-9.
• [2] Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol. 2012 Apr;28(2):69-87.
• [3] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [4] Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells. Toxicol In Vitro. 2020 Feb;62:104669. doi: 10.1016/j.tiv.2019.104669. Epub 2019 Oct 16.
• [5] In vitro metabolism of helenalin and its inhibitory effect on human cytochrome P450 activity. Arch Toxicol. 2022 Mar;96(3):793-808. doi: 10.1007/s00204-021-03218-6. Epub 2022 Jan 6.
• [6] Functional characterization of CYP2A13 polymorphisms. Xenobiotica. 2007 Dec;37(12):1439-49. doi: 10.1080/00498250701666265.
• [7] Oxidation of Flavone, 5-Hydroxyflavone, and 5,7-Dihydroxyflavone to Mono-, Di-, and Tri-Hydroxyflavones by Human Cytochrome P450 Enzymes. Chem Res Toxicol. 2019 Jun 17;32(6):1268-1280. doi: 10.1021/acs.chemrestox.9b00078. Epub 2019 Apr 17.
• [8] Structure-Function Studies of Naphthalene, Phenanthrene, Biphenyl, and Their Derivatives in Interaction with and Oxidation by Cytochromes P450 2A13 and 2A6. Chem Res Toxicol. 2016 Jun 20;29(6):1029-40. doi: 10.1021/acs.chemrestox.6b00083. Epub 2016 May 12.
• [9] Oxidation of Acenaphthene and Acenaphthylene by Human Cytochrome P450 Enzymes. Chem Res Toxicol. 2015 Feb 16;28(2):268-78.