Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRGTS73)

• DOT Name: Dual specificity protein phosphatase 18 (DUSP18)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; Low molecular weight dual specificity phosphatase 20; LMW-DSP20
• Gene Name: DUSP18
• UniProt ID: DUS18_HUMAN
• PDB ID: 2ESB
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MTAPSCAFPVQFRQPSVSGLSQITKSLYISNGVAANNKLMLSSNQITMVINVSVEVVNTL
  YEDIQYMQVPVADSPNSRLCDFFDPIADHIHSVEMKQGRTLLHCAAGVSRSAALCLAYLM
  KYHAMSLLDAHTWTKSCRPIIRPNSGFWEQLIHYEFQLFGKNTVHMVSSPVGMIPDIYEK
  EVRLMIPL
• Function: Can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with preference for the phosphotyrosine and diphosphorylated forms over phosphothreonine. In vitro, dephosphorylates p-nitrophenyl phosphate (pNPP).
• Tissue Specificity: Widely expressed with highest levels in liver, brain, ovary and testis.

Molecular Interaction Atlas (MIA) of This DOT

8 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 Dual specificity protein phosphatase 18 (DUSP18).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dual specificity protein phosphatase 18 (DUSP18).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.