Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6IG629)

• DOT Name: Immediate early response gene 5-like protein (IER5L)
• Gene Name: IER5L
• UniProt ID: IER5L_HUMAN
• Pfam ID: PF05760
• Sequence:
  MECALDAQSLISISLRKIHSSRTQRGGIKLHKNLLVSYVLRNARQLYLSERYAELYRRQQ
  QQQQQQPPHHQHQHLAYAAPGMPASAADFGPLQLGGGGDAEAREPAARHQLHQLHQLHQL
  HLQQQLHQHQHPAPRGCAAAAAAGAPAGGAGALSELPGCAALQPPHGAPHRGQPLEPLQP
  GPAPLPLPLPPPAPAALCPRDPRAPAACSAPPGAAPPAAAASPPASPAPASSPGFYRGAY
  PTPSDFGLHCSSQTTVLDLDTHVVTTVENGYLHQDCCASAHCPCCGQGAPGPGLASAAGC
  KRKYYPGQEEEEDDEEDAGGLGAEPPGGAPFAPCKRARFEDFCPDSSPDASNISNLISIF
  GSGFSGLVSRQPDSSEQPPPLNGQLCAKQALASLGAWTRAIVAF

Molecular Interaction Atlas (MIA) of This DOT

1 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 Immediate early response gene 5-like protein (IER5L).	[1]

20 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 Immediate early response gene 5-like protein (IER5L).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Immediate early response gene 5-like protein (IER5L).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Immediate early response gene 5-like protein (IER5L).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Immediate early response gene 5-like protein (IER5L).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Immediate early response gene 5-like protein (IER5L).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Immediate early response gene 5-like protein (IER5L).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Immediate early response gene 5-like protein (IER5L).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Immediate early response gene 5-like protein (IER5L).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Immediate early response gene 5-like protein (IER5L).	[10]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Immediate early response gene 5-like protein (IER5L).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Immediate early response gene 5-like protein (IER5L).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Immediate early response gene 5-like protein (IER5L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Immediate early response gene 5-like protein (IER5L).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Immediate early response gene 5-like protein (IER5L).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Immediate early response gene 5-like protein (IER5L).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Immediate early response gene 5-like protein (IER5L).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Immediate early response gene 5-like protein (IER5L).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Immediate early response gene 5-like protein (IER5L).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Immediate early response gene 5-like protein (IER5L).	[19]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of Immediate early response gene 5-like protein (IER5L).	[20]

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] 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.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] 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.
• [5] 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.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [11] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] 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.
• [16] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Cytotoxic Effects of Environmental Toxins on Human Glial Cells. Neurotox Res. 2017 Feb;31(2):245-258. doi: 10.1007/s12640-016-9678-5. Epub 2016 Oct 29.