Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK0KCN4)

• DOT Name: EP300-interacting inhibitor of differentiation 2 (EID2)
• Synonyms: EID-2; CREBBP/EP300 inhibitor 2; EID-1-like inhibitor of differentiation 2
• Gene Name: EID2
• UniProt ID: EID2_HUMAN
• Sequence:
  MSKLPADSSVPQTGAANGDRDVPQAEVGRGRREPAPAQPEEAGEGAMAAARGGPVPAARE
  GRMAAARAAPAAAARGAPVAAAALARAAAAGRESPAAAAAREARMAEVARLLGEPVDEEG
  PEGRPRSRHGNGGLAALPYLRLRHPLSVLGINYQQFLRHYLENYPIAPGRIQELEERRRR
  FVEACRAREAAFDAEYQRNPHRVDLDILTFTIALTASEVINPLIEELGCDKFINRE
• Function: Interacts with EP300 and acts as a repressor of MYOD-dependent transcription and muscle differentiation. Inhibits EP300 histone acetyltransferase activity. Acts as a repressor of TGFB/SMAD transcriptional responses. May act as a repressor of the TGFB/SMAD3-dependent signaling by selectively blocking formation of TGFB-induced SMAD3-SMAD4 complex.
• Tissue Specificity: Most abundantly expressed in placenta. Highly expressed in liver, brain, heart, skeletal muscle, and kidney.

Molecular Interaction Atlas (MIA) of This DOT

2 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 EP300-interacting inhibitor of differentiation 2 (EID2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of EP300-interacting inhibitor of differentiation 2 (EID2).	[10]

9 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 2 (EID2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[7]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[9]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of EP300-interacting inhibitor of differentiation 2 (EID2).	[11]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [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] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.