Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT34XWYM)

• DOT Name: Intermediate filament family orphan 2 (IFFO2)
• Gene Name: IFFO2
• Related Disease: Eosinophilic esophagitis
• UniProt ID: IFFO2_HUMAN
• Pfam ID: PF00038
• Sequence:
  MVNSLLFGEMALAFGCPPGGGGGGCPGGGGGGGGAGPGPSPVTAALRDDLGSNIHLLKGL
  NVRFRCFLAKVHELERRNRLLEKQLEQQQSERERRLRYKTFSREQAVQTGPELLRPPAPG
  GGHGLSSGAAAGANANAVALGGLPPGGGSHPQHYGRLPGTIWSYTQVRRTGGGGVETVQG
  PGVSWVHPDGVGVQIDTITPEIRALYNVLAKVKRERDEYKRRWEEELAKRMNLQTMVDTL
  QEAAQEADAIQEEMNEKIERLKAELVVFKGLMSDPMTDLDTKIQEKAMKVDMDICRRIDI
  TAKLCDVAQQRNSEDVSKIFQVVPKKKERKVASDDDISEQDGEVNRFSDDEVGSMNITDE
  MKRMFNQLRETFDFDDDCDSLTWEENEDTLLLWEDFTNCNPTIDLQGEQEENLGNLIHET
  ESFFKTRDKEYQETIGQIELELATAKSDMNRHLHEYMEMCSMKRGLDVQMETCRRLIKGS
  ADRNSPSPSSVASSDSGSTDEIQDEFEREADVEPMVS

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Eosinophilic esophagitis	DISR8WSB	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Intermediate filament family orphan 2 (IFFO2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Intermediate filament family orphan 2 (IFFO2).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Intermediate filament family orphan 2 (IFFO2).	[12]

11 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 Intermediate filament family orphan 2 (IFFO2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Intermediate filament family orphan 2 (IFFO2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Intermediate filament family orphan 2 (IFFO2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Intermediate filament family orphan 2 (IFFO2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Intermediate filament family orphan 2 (IFFO2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Intermediate filament family orphan 2 (IFFO2).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Intermediate filament family orphan 2 (IFFO2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Intermediate filament family orphan 2 (IFFO2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Intermediate filament family orphan 2 (IFFO2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Intermediate filament family orphan 2 (IFFO2).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Intermediate filament family orphan 2 (IFFO2).	[15]

References

• [1] Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.Nat Genet. 2014 Aug;46(8):895-900. doi: 10.1038/ng.3033. Epub 2014 Jul 13.
• [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] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] 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.
• [14] 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.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.