Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3OI5H4)

• DOT Name: EP300-interacting inhibitor of differentiation 1 (EID1)
• Synonyms: 21 kDa pRb-associated protein; CREBBP/EP300 inhibitory protein 1; E1A-like inhibitor of differentiation 1; EID-1
• Gene Name: EID1
• Related Disease:
  Nervous system disease
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Psoriatic arthritis
  Mesothelioma
  Prader-Willi syndrome
  Malignant mesothelioma
  Malignant pleural mesothelioma
• UniProt ID: EID1_HUMAN
• PDB ID: 7SMD
• Sequence:
  MSEMAELSELYEESSDLQMDVMPGEGDLPQMEVGSGSRELSLRPSRSGAQQLEEEGPMEE
  EEAQPMAAPEGKRSLANGPNAGEQPGQVAGADFESEDEGEEFDDWEDDYDYPEEEQLSGA
  GYRVSAALEEADKMFLRTREPALDGGFQMHYEKTPFDQLAFIEELFSLMVVNRLTEELGC
  DEIIDRE
• Function: Interacts with RB1 and EP300 and acts as a repressor of MYOD1 transactivation. Inhibits EP300 and CBP histone acetyltransferase activity. May be involved in coupling cell cycle exit to the transcriptional activation of genes required for cellular differentiation. May act as a candidate coinhibitory factor for NR0B2 that can be directly linked to transcription inhibitory mechanisms.
• Tissue Specificity: Widely expressed. Most abundantly expressed in heart, skeletal muscle, pancreas, brain and testis. Expressed at much lower levels in placenta and peripheral blood leukocyte. Barely detectable in lung. Also weakly expressed in lung carcinoma A-549 and various leukemia cell lines.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[3]
Mesothelioma	DISKWK9M	moderate	Biomarker	[4]
Prader-Willi syndrome	DISYWMLU	moderate	Biomarker	[5]
Malignant mesothelioma	DISTHJGH	Limited	Genetic Variation	[6]
Malignant pleural mesothelioma	DIST2R60	Limited	Altered Expression	[6]

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 EP300-interacting inhibitor of differentiation 1 (EID1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[10]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[13]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[16]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of EP300-interacting inhibitor of differentiation 1 (EID1).	[17]

References

• [1] Transcriptome profiling in Eid1-KO mice brain shows that Eid1 links cell proliferation in the brain.Gene. 2019 Oct 30;717:143998. doi: 10.1016/j.gene.2019.143998. Epub 2019 Aug 2.
• [2] Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease.Neurobiol Dis. 2012 Mar;45(3):902-12. doi: 10.1016/j.nbd.2011.12.007. Epub 2011 Dec 11.
• [3] Usefullnes of atherogenic indices and Ca-LDL level to predict subclinical atherosclerosis in patients with psoriatic arthritis?.Adv Rheumatol. 2019 Nov 14;59(1):49. doi: 10.1186/s42358-019-0096-2.
• [4] Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.Am J Pathol. 2005 Jun;166(6):1827-40. doi: 10.1016/S0002-9440(10)62492-3.
• [5] The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation.Differentiation. 2008 Nov;76(9):994-1005. doi: 10.1111/j.1432-0436.2008.00281.x. Epub 2008 Jun 13.
• [6] Malignant pleural mesothelioma-targeted CREBBP/EP300 inhibitory protein 1 promoter system for gene therapy and virotherapy.Cancer Res. 2008 Sep 1;68(17):7120-9. doi: 10.1158/0008-5472.CAN-08-0047.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [12] 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.
• [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] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [15] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [16] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [17] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.