Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFCF3V5)

• DOT Name: UPF0488 protein C8orf33 (C8ORF33)
• Gene Name: C8ORF33
• Related Disease: Hepatocellular carcinoma
• UniProt ID: CH033_HUMAN
• Pfam ID: PF15393
• Sequence:
  MAALGHLAGEAAAAPGPGTPCASRGARLPGPVSSARNPSTVCLCPEQPTCSNADSRAHPL
  GDEGGTASKKQKNKKKTRNRASVANGGEKASEKLAPEEVPLSAEAQAQQLAQELAWCVEQ
  LELGLKRQKPTPKQKEQAIGAIRTLRSKRTPLPRKRQLMHSLFGDYRAQMEAEWREALRA
  LRAAAYSAQVQPVDGATRKKSQRVCRPRSIWRAKATLDMPDEEFRFNFF

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of UPF0488 protein C8orf33 (C8ORF33).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of UPF0488 protein C8orf33 (C8ORF33).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UPF0488 protein C8orf33 (C8ORF33).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of UPF0488 protein C8orf33 (C8ORF33).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of UPF0488 protein C8orf33 (C8ORF33).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of UPF0488 protein C8orf33 (C8ORF33).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of UPF0488 protein C8orf33 (C8ORF33).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of UPF0488 protein C8orf33 (C8ORF33).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of UPF0488 protein C8orf33 (C8ORF33).	[9]

References

• [1] Deep sequencing and comprehensive expression analysis identifies several molecules potentially related to human poorly differentiated hepatocellular carcinoma.FEBS Open Bio. 2017 Sep 25;7(11):1696-1706. doi: 10.1002/2211-5463.12310. eCollection 2017 Nov.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] 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.