Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ7RCPI)

• DOT Name: Endothelin-2 (EDN2)
• Synonyms: ET-2; Preproendothelin-2; PPET2
• Gene Name: EDN2
• UniProt ID: EDN2_HUMAN
• Pfam ID: PF00322
• Sequence:
  MVSVPTTWCSVALALLVALHEGKGQAAATLEQPASSSHAQGTHLRLRRCSCSSWLDKECV
  YFCHLDIIWVNTPEQTAPYGLGNPPRRRRRSLPRRCQCSSARDPACATFCLRRPWTEAGA
  VPSRKSPADVFQTGKTGATTGELLQRLRDISTVKSLFAKRQQEAMREPRSTHSRWRKR
• Function: Endothelins are endothelium-derived vasoconstrictor peptides.
• Tissue Specificity: Expressed in lung, but not in placental stem villi vessels or cultured placental villi smooth muscle cells.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
  Renin secretion (hsa04924)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Endothelin-2 (EDN2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endothelin-2 (EDN2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Endothelin-2 (EDN2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endothelin-2 (EDN2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Endothelin-2 (EDN2).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Endothelin-2 (EDN2).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Endothelin-2 (EDN2).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Endothelin-2 (EDN2).	[7]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Endothelin-2 (EDN2).	[8]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Endothelin-2 (EDN2).	[9]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid decreases the expression of Endothelin-2 (EDN2).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Endothelin-2 (EDN2).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Endothelin-2 (EDN2).	[3]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Endothelin-2 (EDN2).	[12]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Endothelin-2 (EDN2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Endothelin-2 (EDN2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Endothelin-2 (EDN2).	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Endothelin-2 (EDN2).	[16]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Endothelin-2 (EDN2).	[17]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Application of cDNA microarray to the study of arsenic-induced liver diseases in the population of Guizhou, China. Toxicol Sci. 2001 Jan;59(1):185-92.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [9] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [10] Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis. Aliment Pharmacol Ther. 2005 Feb 1;21(3):227-34. doi: 10.1111/j.1365-2036.2005.02307.x.
• [11] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [12] Genistein affects the expression of genes involved in blood pressure regulation and angiogenesis in primary human endothelial cells. Nutr Metab Cardiovasc Dis. 2006 Jan;16(1):35-43. doi: 10.1016/j.numecd.2005.03.003. Epub 2005 Jul 28.
• [13] Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
• [14] Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
• [15] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [16] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [17] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.