Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRMN4EU)

• DOT Name: COMM domain-containing protein 8 (COMMD8)
• Gene Name: COMMD8
• Related Disease:
  Hepatocellular carcinoma
  Non-small-cell lung cancer
• UniProt ID: COMD8_HUMAN
• PDB ID: 8F2R; 8F2U
• Pfam ID: PF07258
• Sequence:
  MEPEEGTPLWRLQKLPAELGPQLLHKIIDGICGRAYPVYQDYHTVWESEEWMHVLEDIAK
  FFKAIVGKNLPDEEIFQQLNQLNSLHQETIMKCVKSRKDEIKQALSREIVAISSAQLQDF
  DWQVKLALSSDKIAALRMPLLSLHLDVKENGEVKPYSIEMSREELQNLIQSLEAANKVVL
  QLK
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B.
• Tissue Specificity: Widely expressed with highest expression in thyroid.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]

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 COMM domain-containing protein 8 (COMMD8).	[3]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 8 (COMMD8).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of COMM domain-containing protein 8 (COMMD8).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COMM domain-containing protein 8 (COMMD8).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of COMM domain-containing protein 8 (COMMD8).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of COMM domain-containing protein 8 (COMMD8).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of COMM domain-containing protein 8 (COMMD8).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of COMM domain-containing protein 8 (COMMD8).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of COMM domain-containing protein 8 (COMMD8).	[11]

References

• [1] Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis.Biochem Biophys Res Commun. 2019 Jun 4;513(3):669-674. doi: 10.1016/j.bbrc.2019.04.012. Epub 2019 Apr 11.
• [2] Long noncoding RNA LINC00657 induced by SP1 contributes to the non-small cell lung cancer progression through targeting miR-26b-5p/COMMD8 axis.J Cell Physiol. 2020 Apr;235(4):3340-3349. doi: 10.1002/jcp.29222. Epub 2019 Sep 30.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] 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.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.