Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SVTSS)

• DOT Name: Four-jointed box protein 1 (FJX1)
• Synonyms: Four-jointed protein homolog
• Gene Name: FJX1
• Related Disease:
  Acute otitis media
  Advanced cancer
  Brain cancer
  Brain neoplasm
  Colorectal adenoma
  Colorectal carcinoma
  Endometriosis
  Kidney failure
  Nasopharyngeal carcinoma
  Neoplasm
  Polycystic kidney disease 1
  Stickler syndrome type 1
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Rectal carcinoma
• UniProt ID: FJX1_HUMAN
• Sequence:
  MGRRMRGAAATAGLWLLALGSLLALWGGLLPPRTELPASRPPEDRLPRRPARSGGPAPAP
  RFPLPPPLAWDARGGSLKTFRALLTLAAGADGPPRQSRSEPRWHVSARQPRPEESAAVHG
  GVFWSRGLEEQVPPGFSEAQAAAWLEAARGARMVALERGGCGRSSNRLARFADGTRACVR
  YGINPEQIQGEALSYYLARLLGLQRHVPPLALARVEARGAQWAQVQEELRAAHWTEGSVV
  SLTRWLPNLTDVVVPAPWRSEDGRLRPLRDAGGELANLSQAELVDLVQWTDLILFDYLTA
  NFDRLVSNLFSLQWDPRVMQRATSNLHRGPGGALVFLDNEAGLVHGYRVAGMWDKYNEPL
  LQSVCVFRERTARRVLELHRGQDAAARLLRLYRRHEPRFPELAALADPHAQLLQRRLDFL
  AKHILHCKAKYGRRSGT
• Function: Acts as an inhibitor of dendrite extension and branching.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute otitis media	DISL8D8G	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Brain cancer	DISBKFB7	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[3]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Endometriosis	DISX1AG8	Strong	Biomarker	[4]
Kidney failure	DISOVQ9P	Strong	Biomarker	[5]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Polycystic kidney disease 1	DIS9FB3R	Strong	Altered Expression	[6]
Stickler syndrome type 1	DIST5L4S	Strong	Biomarker	[1]
Head and neck cancer	DISBPSQZ	Limited	Altered Expression	[2]
Head and neck carcinoma	DISOU1DS	Limited	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[7]
Rectal carcinoma	DIS8FRR7	Limited	Altered Expression	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Four-jointed box protein 1 (FJX1) affects the response to substance of Topotecan.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Four-jointed box protein 1 (FJX1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Four-jointed box protein 1 (FJX1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Four-jointed box protein 1 (FJX1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Four-jointed box protein 1 (FJX1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Four-jointed box protein 1 (FJX1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Four-jointed box protein 1 (FJX1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Four-jointed box protein 1 (FJX1).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Four-jointed box protein 1 (FJX1).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Four-jointed box protein 1 (FJX1).	[15]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Four-jointed box protein 1 (FJX1).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Four-jointed box protein 1 (FJX1).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Four-jointed box protein 1 (FJX1).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Four-jointed box protein 1 (FJX1).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Four-jointed box protein 1 (FJX1).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Four-jointed box protein 1 (FJX1).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Four-jointed box protein 1 (FJX1).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Four-jointed box protein 1 (FJX1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Four-jointed box protein 1 (FJX1).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Four-jointed box protein 1 (FJX1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Four-jointed box protein 1 (FJX1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Four-jointed box protein 1 (FJX1).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Four-jointed box protein 1 (FJX1).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Four-jointed box protein 1 (FJX1).	[29]

References

• [1] Four jointed box 1 promotes angiogenesis and is associated with poor patient survival in colorectal carcinoma.PLoS One. 2013 Jul 29;8(7):e69660. doi: 10.1371/journal.pone.0069660. Print 2013.
• [2] An Oncogenic Role for Four-Jointed Box 1 (FJX1) in Nasopharyngeal Carcinoma.Dis Markers. 2019 May 19;2019:3857853. doi: 10.1155/2019/3857853. eCollection 2019.
• [3] A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK- and PI3K-induced malignant growth.Dis Model Mech. 2017 Jan 1;10(1):15-28. doi: 10.1242/dmm.026500. Epub 2016 Nov 24.
• [4] Overexpression of Four Joint Box-1 Protein (FJX1) in Eutopic Endometrium From Women With Endometriosis.Reprod Sci. 2018 Feb;25(2):207-213. doi: 10.1177/1933719117716780. Epub 2017 Jul 4.
• [5] Four-jointed knock-out delays renal failure in an ADPKD model with kidney injury.J Pathol. 2019 Sep;249(1):114-125. doi: 10.1002/path.5286. Epub 2019 Jun 17.
• [6] Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways.Hum Mol Genet. 2009 Jul 15;18(14):2532-42. doi: 10.1093/hmg/ddp190. Epub 2009 Apr 28.
• [7] In vitro evaluation of dual-antigenic PV1 peptide vaccine in head and neck cancer patients.Hum Vaccin Immunother. 2019;15(1):167-178. doi: 10.1080/21645515.2018.1520584. Epub 2018 Oct 12.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [15] 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.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [19] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] 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.
• [22] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [23] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [24] 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.
• [25] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [28] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [29] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [30] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.