Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU7LW2F)

• DOT Name: Epoxide hydrolase 3 (EPHX3)
• Synonyms: EH3; EC 3.3.2.10; Abhydrolase domain-containing protein 9
• Gene Name: EPHX3
• Related Disease:
  Carcinoma
  Melanoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
• UniProt ID: EPHX3_HUMAN
• EC Number: 3.3.2.10
• Pfam ID: PF00561
• Sequence:
  MPELVVTALLAPSRLSLKLLRAFMWSLVFSVALVAAAVYGCIALTHVLCRPRRGCCGRRR
  SASPACLSDPSLGEHGFLNLKSSGLRLHYVSAGRGNGPLMLFLHGFPENWFSWRYQLREF
  QSRFHVVAVDLRGYGPSDAPRDVDCYTIDLLLVDIKDVILGLGYSKCILVAHDWGALLAW
  HFSIYYPSLVERMVVVSGAPMSVYQDYSLHHISQFFRSHYMFLFQLPWLPEKLLSMSDFQ
  ILKTTLTHRKTGIPCLTPSELEAFLYNFSQPGGLTGPLNYYRNLFRNFPLEPQELTTPTL
  LLWGEKDTYLELGLVEAIGSRFVPGRLEAHILPGIGHWIPQSNPQEMHQYMWAFLQDLLD
• Function: Catalyzes the hydrolysis of epoxide-containing fatty acids. Active in vitro against epoxyeicosatrienoic acids (EETs) including 8,9-EET, 9,10-EET, 11,12-EET and 14,15-EET and leukotoxin.
• KEGG Pathway:
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• BioCyc Pathway: MetaCyc:ENSG00000105131-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Posttranslational Modification	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[4]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Epoxide hydrolase 3 (EPHX3).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Epoxide hydrolase 3 (EPHX3).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Epoxide hydrolase 3 (EPHX3).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Epoxide hydrolase 3 (EPHX3).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Epoxide hydrolase 3 (EPHX3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Epoxide hydrolase 3 (EPHX3).	[9]

References

• [1] Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas.Int J Cancer. 2011 Dec 15;129(12):2855-66. doi: 10.1002/ijc.25951. Epub 2011 Apr 1.
• [2] Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.Cancer Res. 2006 Jun 15;66(12):6080-6. doi: 10.1158/0008-5472.CAN-06-0157.
• [3] Discovery and validation of 3 novel DNA methylation markers of prostate cancer prognosis.J Urol. 2007 May;177(5):1753-8. doi: 10.1016/j.juro.2007.01.010.
• [4] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [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] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.