Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3EXB6S)

• DOT Name: Probable RNA-binding protein EIF1AD (EIF1AD)
• Synonyms: Eukaryotic translation initiation factor 1A domain-containing protein; Haponin
• Gene Name: EIF1AD
• Related Disease: Melanoma
• UniProt ID: EIF1A_HUMAN
• PDB ID: 2DGY; 6ZXF; 6ZXG; 6ZXH
• Pfam ID: PF01176
• Sequence:
  MSQATKRKHVVKEVLGEHIVPSDQQQIVRVLRTPGNNLHEVETAQGQRFLVSMPSKYRKN
  IWIKRGDFLIVDPIEEGEKVKAEISFVLCKDHVRSLQKEGFWPEAFSEVAEKHNNRNRQT
  QPELPAEPQLSGEESSSEDDSDLFVNTNRRQYHESEEESEEEEAA
• Function: Plays a role into cellular response to oxidative stress. Decreases cell proliferation.
• Tissue Specificity: Expressed in the glioblastoma cell line U-87MG, the embryonic kidney cell line HEK293, the pancreatic carcinoma cell line PANC-1, the breast carcinoma cell line MCF-7, the lung cancer cell line NCI-H460, and the chronic myelogenous leukemia cell line K-562.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Probable RNA-binding protein EIF1AD (EIF1AD).	[10]

References

• [1] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.