Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHW01L0)

• DOT Name: Uncharacterized protein C8orf58 (C8ORF58)
• Gene Name: C8ORF58
• UniProt ID: CH058_HUMAN
• Pfam ID: PF15552
• Sequence:
  MMGRRRAFAVDGRDGAGEGLARGCIVPGVTSTYRRIPDAAHGCSSWERGDKFRGVGREAL
  FLKLASRDSGVEMAVGDSPLAALPGLSQDSLDFESSGSSEPPAQVGRLLASQKLGEVLER
  SRRLPTAPTSLSGQHRSLRLASKPEREVPLGAGQQESMEADTDLEAGLEEEAVGGLGPGA
  WACLPGQGLRYLEHLCLVLEQMARLQQLYLQLRIQRPPGDPGEEESTRAPLPSPLHTPGN
  RGQGPWELLSQTEHTGAKAASPPKVEVPSANPPRLPETPVEPTYHLPSSQGHKRDISHWD
  KVKVLLNRICRRSHHHPEPPAPPDGSDPRIESRDLPERPQCRPHRKTFMPSLVVKKQRAK
  NLSVG

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 Uncharacterized protein C8orf58 (C8ORF58).	[1]

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 Uncharacterized protein C8orf58 (C8ORF58).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Uncharacterized protein C8orf58 (C8ORF58).	[5]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Uncharacterized protein C8orf58 (C8ORF58).	[12]

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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.