Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE2PG54)

• DOT Name: Dual specificity protein phosphatase 23 (DUSP23)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; Low molecular mass dual specificity phosphatase 3; LDP-3; VH1-like phosphatase Z
• Gene Name: DUSP23
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
  Systemic lupus erythematosus
  Neuroblastoma
• UniProt ID: DUS23_HUMAN
• PDB ID: 2IMG; 4ERC
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MGVQPPNFSWVLPGRLAGLALPRLPAHYQFLLDLGVRHLVSLTERGPPHSDSCPGLTLHR
  LRIPDFCPPAPDQIDRFVQIVDEANARGEAVGVHCALGFGRTGTMLACYLVKERGLAAGD
  AIAEIRRLRPGSIETYEQEKAVFQFYQRTK
• Function: Protein phosphatase that mediates dephosphorylation of proteins phosphorylated on Tyr and Ser/Thr residues. In vitro, it can dephosphorylate p44-ERK1 (MAPK3) but not p54 SAPK-beta (MAPK10) in vitro. Able to enhance activation of JNK and p38 (MAPK14).
• Tissue Specificity: Widely expressed. Highly expressed in spleen, prostate, colon, adrenal gland, mammary gland, thyroid and trachea. Expressed at lower level in uterus, small intestine, bladder, bone marrow, brain, spinal cord and stomach.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[2]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[3]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-nitrophenyl phosphate	DMBX4UJ	Investigative	Dual specificity protein phosphatase 23 (DUSP23) decreases the phosphorylation of 4-nitrophenyl phosphate.	[10]

6 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 23 (DUSP23).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dual specificity protein phosphatase 23 (DUSP23).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dual specificity protein phosphatase 23 (DUSP23).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Dual specificity protein phosphatase 23 (DUSP23).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dual specificity protein phosphatase 23 (DUSP23).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dual specificity protein phosphatase 23 (DUSP23).	[9]

References

• [1] VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.Mol Cancer. 2010 May 28;9:128. doi: 10.1186/1476-4598-9-128.
• [2] DUSP23 is over-expressed and linked to the expression of DNMTs in CD4(+) T cells from systemic lupus erythematosus patients.Clin Exp Immunol. 2017 Feb;187(2):242-250. doi: 10.1111/cei.12883. Epub 2016 Nov 16.
• [3] Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma.BMC Cancer. 2011 Feb 11;11:66. doi: 10.1186/1471-2407-11-66.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [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] Molecular cloning and characterization of a novel dual-specificity phosphatase 23 gene from human fetal brain. Int J Biochem Cell Biol. 2004 Aug;36(8):1542-53. doi: 10.1016/j.biocel.2003.12.014.