Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAND0C7)

• DOT Name: EP300-interacting inhibitor of differentiation 3 (EID3)
• Synonyms: EID-3; E1A-like inhibitor of differentiation 3; EID-1-like inhibitor of differentiation 3; Non-structural maintenance of chromosomes element 4 homolog B; NS4EB; Non-SMC element 4 homolog B
• Gene Name: EID3
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
  Neuroendocrine neoplasm
• UniProt ID: EID3_HUMAN
• Pfam ID: PF15412 ; PF08743
• Sequence:
  MKMDVSVRAAGCSDDLSSGEADVDPKLLELTADEEKCRSIRRQYRQLMYCVRQNREDIVS
  SANNSLTEALEEANVLFDGVSRTREAALDARFLVMASDLGKEKAKQLNSDMNFFNQLAFC
  DFLFLFVGLNWMEGDPDKLSDCDDSIALSFWKAIEKEATSWMVKAETFHFVFGSFKLERS
  APKPRLEHQKKVRKMEENGNMPTKLQKLDLSSYPEATEKNVERILGLLQTYFRKYPDTPV
  SYFEFVIDPNSFSRTVENIFYVSFIVRDGFARIRLDEDRLPILEPMNVNQMGEGNDSSCH
  GRKQGVISLTLQEWKNIVAAFEISEAMITYSSY
• Function: Tissue-specific component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components; Acts as a repressor of nuclear receptor-dependent transcription possibly by interfering with CREBBP-dependent coactivation. May function as a coinhibitor of other CREBBP/EP300-dependent transcription factors.
• Tissue Specificity: Highly expressed in testis.
• Reactome Pathway: SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[2]

14 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 EP300-interacting inhibitor of differentiation 3 (EID3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[7]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[15]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of EP300-interacting inhibitor of differentiation 3 (EID3).	[16]

1 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 EP300-interacting inhibitor of differentiation 3 (EID3).	[11]

References

• [1] Upregulation of EID3 sensitizes breast cancer cells to ionizing radiation-induced cellular senescence.Biomed Pharmacother. 2018 Nov;107:606-614. doi: 10.1016/j.biopha.2018.08.022. Epub 2018 Aug 14.
• [2] Identification of novel serum autoantibodies against EID3 in non-functional pancreatic neuroendocrine tumors.Oncotarget. 2017 Oct 31;8(63):106206-106221. doi: 10.18632/oncotarget.22175. eCollection 2017 Dec 5.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [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] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [16] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.