Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXAUJ47)

• DOT Name: Forkhead box protein J3 (FOXJ3)
• Gene Name: FOXJ3
• Related Disease:
  Non-small-cell lung cancer
  Rheumatoid arthritis
• UniProt ID: FOXJ3_HUMAN
• Pfam ID: PF00250
• Sequence:
  MGLYGQACPSVTSLRMTSELESSLTSMDWLPQLTMRAAIQKSDATQNAHGTGISKKNALL
  DPNTTLDQEEVQQHKDGKPPYSYASLITFAINSSPKKKMTLSEIYQWICDNFPYYREAGS
  GWKNSIRHNLSLNKCFLKVPRSKDDPGKGSYWAIDTNPKEDVLPTRPKKRARSVERASTP
  YSIDSDSLGMECIISGSASPTLAINTVTNKVTLYNTDQDGSDSPRSSLNNSLSDQSLASV
  NLNSVGSVHSYTPVTSHPESVSQSLTPQQQPQYNLPERDKQLLFSEYNFEDLSASFRSLY
  KSVFEQSLSQQGLMNIPSESSQQSHTSCTYQHSPSSTVSTHPHSNQSSLSNSHGSGLNTT
  GSNSVAQVSLSHPQMHTQPSPHPPHRPHGLPQHPQRSPHPAPHPQQHSQLQSPHPQHPSP
  HQHIQHHPNHQHQTLTHQAPPPPQQVSCNSGVSNDWYATLDMLKESCRIASSVNWSDVDL
  SQFQGLMESMRQADLKNWSLDQVQFADLCSSLNQFFTQTGLIHSQSNVQQNVCHGAMHPT
  KPSQHIGTGNLYIDSRQNLPPSVMPPPGYPHIPQALSTPGTTMAGHHRAMNQQHMMPSQA
  FQMRRSLPPDDIQDDFDWDSIV
• Function: Transcriptional activator of MEF2C involved in the regulation of adult muscle fiber type identity and skeletal muscle regeneration. Plays an important role in spermatogenesis. Required for the survival of spermatogonia and participates in spermatocyte meiosis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[2]

11 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 J3 (FOXJ3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Forkhead box protein J3 (FOXJ3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Forkhead box protein J3 (FOXJ3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Forkhead box protein J3 (FOXJ3).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Forkhead box protein J3 (FOXJ3).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Forkhead box protein J3 (FOXJ3).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Forkhead box protein J3 (FOXJ3).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Forkhead box protein J3 (FOXJ3).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Forkhead box protein J3 (FOXJ3).	[12]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Forkhead box protein J3 (FOXJ3).	[15]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Forkhead box protein J3 (FOXJ3).	[16]

3 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 J3 (FOXJ3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Forkhead box protein J3 (FOXJ3).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Forkhead box protein J3 (FOXJ3).	[14]

References

• [1] Overexpression of miR-425-5p is associated with poor prognosis and tumor progression in non-small cell lung cancer.Cancer Biomark. 2020;27(2):147-156. doi: 10.3233/CBM-190782.
• [2] Association of forkhead box J3 (FOXJ3) polymorphisms with rheumatoid arthritis.Mol Med Rep. 2013 Oct;8(4):1235-41. doi: 10.3892/mmr.2013.1623. Epub 2013 Aug 9.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Distinct genetic profile in peripheral blood mononuclear cells of psoriatic arthritis patients treated with methotrexate and TNF-inhibitors. Clin Rheumatol. 2014 Dec;33(12):1815-21. doi: 10.1007/s10067-014-2807-8. Epub 2014 Oct 24.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [16] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.