Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPJX9B4)

• DOT Name: Dual specificity protein phosphatase 3 (DUSP3)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; Dual specificity protein phosphatase VHR; Vaccinia H1-related phosphatase; VHR
• Gene Name: DUSP3
• UniProt ID: DUS3_HUMAN
• PDB ID: 1J4X; 1VHR; 3F81
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MSGSFELSVQDLNDLLSDGSGCYSLPSQPCNEVTPRIYVGNASVAQDIPKLQKLGITHVL
  NAAEGRSFMHVNTNANFYKDSGITYLGIKANDTQEFNLSAYFERAADFIDQALAQKNGRV
  LVHCREGYSRSPTLVIAYLMMRQKMDVKSALSIVRQNREIGPNDGFLAQLCQLNDRLAKE
  GKLKP
• Function: Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.
• KEGG Pathway: MAPK sig.ling pathway (hsa04010)
• Reactome Pathway: ERKs are inactivated (R-HSA-202670)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Dual specificity protein phosphatase 3 (DUSP3) affects the response to substance of Topotecan.	[17]
Gefitinib	DM15F0X	Approved	Dual specificity protein phosphatase 3 (DUSP3) affects the response to substance of Gefitinib.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Dual specificity protein phosphatase 3 (DUSP3).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Dual specificity protein phosphatase 3 (DUSP3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Dual specificity protein phosphatase 3 (DUSP3).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Dual specificity protein phosphatase 3 (DUSP3).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Dual specificity protein phosphatase 3 (DUSP3).	[8]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Dual specificity protein phosphatase 3 (DUSP3).	[16]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Dual specificity protein phosphatase 3 (DUSP3).	[12]

References

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• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [12] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] 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.
• [15] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [17] 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.
• [18] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.