Details of Drug Off-Target (DOT)

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

• DOT Name: Forkhead box protein N2 (FOXN2)
• Synonyms: Human T-cell leukemia virus enhancer factor
• Gene Name: FOXN2
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Breast cancer
  Breast carcinoma
• UniProt ID: FOXN2_HUMAN
• Pfam ID: PF00250
• Sequence:
  MGPVIGMTPDKRAETPGAEKIAGLSQIYKMGSLPEAVDAARPKATLVDSESADDELTNLN
  WLHESTNLLTNFSLGSEGLPIVSPLYDIEGDDVPSFGPACYQNPEKKSATSKPPYSFSLL
  IYMAIEHSPNKCLPVKEIYSWILDHFPYFATAPTGWKNSVRHNLSLNKCFQKVERSHGKV
  NGKGSLWCVDPEYKPNLIQALKKQPFSSASSQNGSLSPHYLSSVIKQNQVRNLKESDIDA
  AAAMMLLNTSIEQGILECEKPLPLKTALQKKRSYGNAFHHPSAVRLQESDSLATSIDPKE
  DHNYSASSMAAQRCASRSSVSSLSSVDEVYEFIPKNSHVGSDGSEGFHSEEDTDVDYEDD
  PLGDSGYASQPCAKISEKGQSGKKMRKQTCQEIDEELKEAAGSLLHLAGIRTCLGSLIST
  AKTQNQKQRKK
• Function: Binds to the purine-rich region in HTLV-I LTR.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	moderate	Biomarker	[3]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Forkhead box protein N2 (FOXN2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Forkhead box protein N2 (FOXN2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Forkhead box protein N2 (FOXN2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Forkhead box protein N2 (FOXN2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Forkhead box protein N2 (FOXN2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Forkhead box protein N2 (FOXN2).	[10]

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 Forkhead box protein N2 (FOXN2).	[8]

References

• [1] Chromosomal imbalances in adult T-cell leukemia revealed by comparative genomic hybridization: gains at 14q32 and 2p16-22 in cell lines.J Hum Genet. 1999;44(6):357-63. doi: 10.1007/s100380050178.
• [2] -Trcp ubiquitin ligase and RSK2 kinase-mediated degradation of FOXN2 promotes tumorigenesis and radioresistance in lung cancer.Cell Death Differ. 2018 Aug;25(8):1473-1485. doi: 10.1038/s41418-017-0055-6. Epub 2018 Feb 2.
• [3] FOXN2 is downregulated in breast cancer and regulates migration, invasion, and epithelial- mesenchymal transition through regulation of SLUG.Cancer Manag Res. 2019 Jan 4;11:525-535. doi: 10.2147/CMAR.S176938. eCollection 2019.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.