Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTECTJ7K)

• DOT Name: Epidermal growth factor-like protein 8 (EGFL8)
• Synonyms: EGF-like protein 8; Vascular endothelial statin-2; VE-statin-2
• Gene Name: EGFL8
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Membranous glomerulonephritis
  Rheumatoid arthritis
  Vitiligo
  Carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: EGFL8_HUMAN
• Pfam ID: PF00008 ; PF07645 ; PF07546
• Sequence:
  MGSRAELCTLLGGFSFLLLLIPGEGAKGGSLRESQGVCSKQTLVVPLHYNESYSQPVYKP
  YLTLCAGRRICSTYRTMYRVMWREVRREVQQTHAVCCQGWKKRHPGALTCEAICAKPCLN
  GGVCVRPDQCECAPGWGGKHCHVDVDECRTSITLCSHHCFNTAGSFTCGCPHDLVLGVDG
  RTCMEGSPEPPTSASILSVAVREAEKDERALKQEIHELRGRLERLEQWAGQAGAWVRAVL
  PVPPEELQPEQVAELWGRGDRIESLSDQVLLLEERLGACSCEDNSLGLGVNHR

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]
Vitiligo	DISR05SL	Strong	Genetic Variation	[4]
Carcinoma	DISH9F1N	Disputed	Altered Expression	[1]
Gastric cancer	DISXGOUK	Disputed	Altered Expression	[1]
Stomach cancer	DISKIJSX	Disputed	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Epidermal growth factor-like protein 8 (EGFL8) affects the response to substance of Etoposide.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Epidermal growth factor-like protein 8 (EGFL8).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Epidermal growth factor-like protein 8 (EGFL8).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Epidermal growth factor-like protein 8 (EGFL8).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Epidermal growth factor-like protein 8 (EGFL8).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Epidermal growth factor-like protein 8 (EGFL8).	[10]

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 Epidermal growth factor-like protein 8 (EGFL8).	[7]

References

• [1] Down-regulation of EGFL8: a novel biomarker for advanced gastric cancer.Anticancer Res. 2011 Oct;31(10):3377-80.
• [2] Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
• [3] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [4] Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.Nat Genet. 2010 Jul;42(7):614-8. doi: 10.1038/ng.603. Epub 2010 Jun 6.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] 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.
• [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 profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.