Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAHO1ZC)

• DOT Name: FGFR1 oncogene partner 2 (FGFR1OP2)
• Gene Name: FGFR1OP2
• Related Disease: Myeloproliferative neoplasm
• UniProt ID: FGOP2_HUMAN
• Pfam ID: PF05769
• Sequence:
  MSCTIEKALADAKALVERLRDHDDAAESLIEQTTALNKRVEAMKQYQEEIQELNEVARHR
  PRSTLVMGIQQENRQIRELQQENKELRTSLEEHQSALELIMSKYREQMFRLLMASKKDDP
  GIIMKLKEQHSKIDMVHRNKSEGFFLDASRHILEAPQHGLERRHLEANQNELQAHVDQIT
  EMAAVMRKAIEIDEQQGCKEQERIFQLEQENKGLREILQITRESFLNLRKDDASESTSLS
  ALVTNSDLSLRKS
• Function: May be involved in wound healing pathway.
• Tissue Specificity: Expressed in bone marrow, spleen and thymus.
• Reactome Pathway:
  Signaling by FGFR1 in disease (R-HSA-5655302)
  Signaling by cytosolic FGFR1 fusion mutants (R-HSA-1839117)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myeloproliferative neoplasm	DIS5KAPA	Limited	Genetic Variation	[1]

4 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 FGFR1 oncogene partner 2 (FGFR1OP2).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of FGFR1 oncogene partner 2 (FGFR1OP2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of FGFR1 oncogene partner 2 (FGFR1OP2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of FGFR1 oncogene partner 2 (FGFR1OP2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of FGFR1 oncogene partner 2 (FGFR1OP2).	[18]

References

• [1] The driver of malignancy in KG-1a leukemic cells, FGFR1OP2-FGFR1, encodes an HSP90 addicted oncoprotein.Cell Signal. 2011 Nov;23(11):1758-66. doi: 10.1016/j.cellsig.2011.06.010. Epub 2011 Jun 30.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] 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.
• [15] 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.
• [16] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.