Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNFK6R)

• DOT Name: UPF0561 protein C2orf68 (C2ORF68)
• Gene Name: C2ORF68
• Related Disease:
  Colon carcinoma
  Rectal carcinoma
  Advanced cancer
  Colorectal carcinoma
• UniProt ID: CB068_HUMAN
• Pfam ID: PF10573
• Sequence:
  MEAGPHPRPGHCCKPGGRLDMNHGFVHHIRRNQIARDDYDKKVKQAAKEKVRRRHTPAPT
  RPRKPDLQVYLPRHRDVSAHPRNPDYEESGESSSSGGSELEPSGHQLFCLEYEADSGEVT
  SVIVYQGDDPGKVSEKVSAHTPLDPPMREALKLRIQEEIAKRQSQH

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Rectal carcinoma	DIS8FRR7	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[2]

10 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 UPF0561 protein C2orf68 (C2ORF68).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of UPF0561 protein C2orf68 (C2ORF68).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of UPF0561 protein C2orf68 (C2ORF68).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of UPF0561 protein C2orf68 (C2ORF68).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of UPF0561 protein C2orf68 (C2ORF68).	[8]

References

• [1] Hcrcn81 is upregulated by rapamycin treatment in human colorectal adenocarcinoma cells.Mol Med Rep. 2013 Apr;7(4):1257-60. doi: 10.3892/mmr.2013.1317. Epub 2013 Feb 8.
• [2] Interaction between C2ORF68 and HuR in human colorectal cancer.Oncol Rep. 2019 Mar;41(3):1918-1928. doi: 10.3892/or.2019.6973. Epub 2019 Jan 21.
• [3] The role of c2orf68 and PI3K/Akt/mTOR pathway in human colorectal cancer.Med Oncol. 2014 Aug;31(8):92. doi: 10.1007/s12032-014-0092-7. Epub 2014 Jul 15.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] 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.