Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK0NFXJ)

• DOT Name: Protein tyrosine phosphatase type IVA 1 (PTP4A1)
• Synonyms: EC 3.1.3.48; PTP(CAAXI); Protein-tyrosine phosphatase 4a1; Protein-tyrosine phosphatase of regenerating liver 1; PRL-1
• Gene Name: PTP4A1
• UniProt ID: TP4A1_HUMAN
• PDB ID: 1RXD; 1XM2; 5BX1
• EC Number: 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MARMNRPAPVEVTYKNMRFLITHNPTNATLNKFIEELKKYGVTTIVRVCEATYDTTLVEK
  EGIHVLDWPFDDGAPPSNQIVDDWLSLVKIKFREEPGCCIAVHCVAGLGRAPVLVALALI
  EGGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFKDSNGHRNNCCIQ
• Function: Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. May play a role in the development and maintenance of differentiating epithelial tissues. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis.
• Tissue Specificity: Expressed in bone marrow, lymph nodes, T lymphocytes, spleen, thymus and tonsil. Overexpressed in tumor cell lines.

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 Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[9]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[10]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[11]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[3]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[3]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[16]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[17]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[21]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[22]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the expression of Protein tyrosine phosphatase type IVA 1 (PTP4A1).	[23]

References

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• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] DNA array analysis of the effects of aspirin on colon cancer cells: involvement of Rac1. Carcinogenesis. 2004 Jul;25(7):1293-8.
• [11] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
• [18] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [19] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [23] Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis. 2006 Oct;27(10):1950-60.