Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2KAOBA)

• DOT Name: Ergosterol biosynthetic protein 28 homolog (ERG28)
• Gene Name: ERG28
• UniProt ID: ERG28_HUMAN
• Pfam ID: PF03694
• Sequence:
  MSRFLNVLRSWLVMVSIIAMGNTLQSFRDHTFLYEKLYTGKPNLVNGLQARTFGIWTLLS
  SVIRCLCAIDIHNKTLYHITLWTFLLALGHFLSELFVYGTAAPTIGVLAPLMVASFSILG
  MLVGLRYLEVEPVSRQKKRN
• Tissue Specificity: Ubiquitous; strongly expressed in testis and some cancer cell lines.

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 decreases the methylation of Ergosterol biosynthetic protein 28 homolog (ERG28).	[1]

19 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 Ergosterol biosynthetic protein 28 homolog (ERG28).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[11]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[12]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[19]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Ergosterol biosynthetic protein 28 homolog (ERG28).	[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] 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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005 Feb 1;105(3):1214-21. doi: 10.1182/blood-2004-03-1182. Epub 2004 Sep 28.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [13] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [16] 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.
• [17] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis. 2006 Oct;27(10):1950-60.