Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY3HJH1)

• DOT Name: Cytochrome P450 2F1 (CYP2F1)
• Synonyms: EC 1.14.14.1; CYPIIF1
• Gene Name: CYP2F1
• UniProt ID: CP2F1_HUMAN
• EC Number: 1.14.14.1
• Pfam ID: PF00067
• Sequence:
  MDSISTAILLLLLALVCLLLTLSSRDKGKLPPGPRPLSILGNLLLLCSQDMLTSLTKLSK
  EYGSMYTVHLGPRRVVVLSGYQAVKEALVDQGEEFSGRGDYPAFFNFTKGNGIAFSSGDR
  WKVLRQFSIQILRNFGMGKRSIEERILEEGSFLLAELRKTEGEPFDPTFVLSRSVSNIIC
  SVLFGSRFDYDDERLLTIIRLINDNFQIMSSPWGELYDIFPSLLDWVPGPHQRIFQNFKC
  LRDLIAHSVHDHQASLDPRSPRDFIQCFLTKMAEEKEDPLSHFHMDTLLMTTHNLLFGGT
  KTVSTTLHHAFLALMKYPKVQARVQEEIDLVVGRARLPALKDRAAMPYTDAVIHEVQRFA
  DIIPMNLPHRVTRDTAFRGFLIPKGTDVITLLNTVHYDPSQFLTPQEFNPEHFLDANQSF
  KKSPAFMPFSAGRRLCLGESLARMELFLYLTAILQSFSLQPLGAPEDIDLTPLSSGLGNL
  PRPFQLCLRPR
• Function: May be involved in the metabolism of various pneumotoxicants including naphthalene. Is able to dealkylate ethoxycoumarin, propoxycoumarin, and pentoxyresorufin but possesses no activity toward ethoxyresorufin and only trace dearylation activity toward benzyloxyresorufin. Bioactivates 3-methylindole (3MI) by dehydrogenation to the putative electrophile 3-methylene-indolenine.
• Tissue Specificity: Expressed in lung. Rarely detected in liver and placenta.
• KEGG Pathway:
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway:
  Xenobiotics (R-HSA-211981)
  CYP2E1 reactions (R-HSA-211999)
  Fatty acids (R-HSA-211935)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytochrome P450 2F1 (CYP2F1).	[1]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Cytochrome P450 2F1 (CYP2F1).	[2]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Cytochrome P450 2F1 (CYP2F1).	[3]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Cytochrome P450 2F1 (CYP2F1).	[2]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Cytochrome P450 2F1 (CYP2F1).	[4]

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 2F1 (CYP2F1).	[5]

References

• [1] Human drug metabolism genes in parathion-and estrogen-treated breast cells. Int J Mol Med. 2007 Dec;20(6):875-81.
• [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] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [4] Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
• [5] 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.