Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO4ZVIA)

• DOT Name: Tyrosine-protein phosphatase non-receptor type 1 (PTPN1)
• Synonyms: EC 3.1.3.48; Protein-tyrosine phosphatase 1B; PTP-1B
• Gene Name: PTPN1
• UniProt ID: PTN1_HUMAN
• PDB ID: 1A5Y ; 1AAX ; 1BZC ; 1BZH ; 1BZJ ; 1C83 ; 1C84 ; 1C85 ; 1C86 ; 1C87 ; 1C88 ; 1ECV ; 1EEN ; 1EEO ; 1G1F ; 1G1G ; 1G1H ; 1G7F ; 1G7G ; 1GFY ; 1I57 ; 1JF7 ; 1KAK ; 1KAV ; 1L8G ; 1LQF ; 1NL9 ; 1NNY ; 1NO6 ; 1NWE ; 1NWL ; 1NZ7 ; 1OEM ; 1OEO ; 1OES ; 1OET ; 1OEU ; 1OEV ; 1ONY ; 1ONZ ; 1PA1 ; 1PH0 ; 1PTT ; 1PTU ; 1PTV ; 1PTY ; 1PXH ; 1PYN ; 1Q1M ; 1Q6J ; 1Q6M ; 1Q6N ; 1Q6P ; 1Q6S ; 1Q6T ; 1QXK ; 1SUG ; 1T48 ; 1T49 ; 1T4J ; 1WAX ; 1XBO ; 2AZR ; 2B07 ; 2B4S ; 2BGD ; 2BGE ; 2CM2 ; 2CM3 ; 2CM7 ; 2CM8 ; 2CMA ; 2CMB ; 2CMC ; 2CNE ; 2CNF ; 2CNG ; 2CNH ; 2CNI ; 2F6F ; 2F6T ; 2F6V ; 2F6W ; 2F6Y ; 2F6Z ; 2F70 ; 2F71 ; 2FJM ; 2FJN ; 2H4G ; 2H4K ; 2HB1 ; 2HNP ; 2HNQ ; 2NT7 ; 2NTA ; 2QBP ; 2QBQ ; 2QBR ; 2QBS ; 2VEU ; 2VEV ; 2VEW ; 2VEX ; 2VEY ; 2ZMM ; 2ZN7 ; 3A5J ; 3A5K ; 3CWE ; 3D9C ; 3EAX ; 3EB1 ; 3EU0 ; 3I7Z ; 3I80 ; 3QKP ; 3QKQ ; 3SME ; 3ZMP ; 3ZMQ ; 3ZV2 ; 4BJO ; 4I8N ; 4QAH ; 4QAP ; 4QBE ; 4QBW ; 4Y14 ; 4ZRT ; 5K9V ; 5K9W ; 5KA0 ; 5KA1 ; 5KA2 ; 5KA3 ; 5KA4 ; 5KA7 ; 5KA8 ; 5KA9 ; 5KAA ; 5KAB ; 5KAC ; 5KAD ; 5QDE ; 5QDF ; 5QDG ; 5QDH ; 5QDI ; 5QDJ ; 5QDK ; 5QDL ; 5QDM ; 5QDN ; 5QDO ; 5QDP ; 5QDQ ; 5QDR ; 5QDS ; 5QDT ; 5QDU ; 5QDV ; 5QDW ; 5QDX ; 5QDY ; 5QDZ ; 5QE0 ; 5QE1 ; 5QE2 ; 5QE3 ; 5QE4 ; 5QE5 ; 5QE6 ; 5QE7 ; 5QE8 ; 5QE9 ; 5QEA ; 5QEB ; 5QEC ; 5QED ; 5QEE ; 5QEF ; 5QEG ; 5QEH ; 5QEI ; 5QEJ ; 5QEK ; 5QEL ; 5QEM ; 5QEN ; 5QEO ; 5QEP ; 5QEQ ; 5QER ; 5QES ; 5QET ; 5QEU ; 5QEV ; 5QEW ; 5QEX ; 5QEY ; 5QEZ ; 5QF0 ; 5QF1 ; 5QF2 ; 5QF3 ; 5QF4 ; 5QF5 ; 5QF6 ; 5QF7 ; 5QF8 ; 5QF9 ; 5QFA ; 5QFB ; 5QFC ; 5QFD ; 5QFE ; 5QFF ; 5QFG ; 5QFH ; 5QFI ; 5QFJ ; 5QFK ; 5QFL ; 5QFM ; 5QFN ; 5QFO ; 5QFP ; 5QFQ ; 5QFR ; 5QFS ; 5QFT ; 5QFU ; 5QFV ; 5QFW ; 5QFX ; 5QFY ; 5QFZ ; 5QG0 ; 5QG1 ; 5QG2 ; 5QG3 ; 5QG4 ; 5QG5 ; 5QG6 ; 5QG7 ; 5QG8 ; 5QG9 ; 5QGA ; 5QGB ; 5QGC ; 5QGD ; 5QGE ; 5QGF ; 5T19 ; 6B8E ; 6B8T ; 6B8X ; 6B8Z ; 6B90 ; 6B95 ; 6BAI ; 6CWU ; 6CWV ; 6NTP ; 6OL4 ; 6OLQ ; 6OLV ; 6OMY ; 6PFW ; 6PG0 ; 6PGT ; 6PHA ; 6PHS ; 6PM8 ; 6W30 ; 6XE8 ; 6XEA ; 6XED ; 6XEE ; 6XEF ; 6XEG ; 7FQM ; 7FQN ; 7FQO ; 7FQP ; 7FQQ ; 7FQR ; 7FQS ; 7FQT ; 7FQU ; 7FQV ; 7FQW ; 7FQX ; 7FQY ; 7FQZ ; 7FRE ; 7FRF ; 7FRG ; 7FRH ; 7FRI ; 7FRJ ; 7FRK ; 7FRL ; 7FRM ; 7FRN ; 7FRO ; 7FRP ; 7FRQ ; 7FRR ; 7FRS ; 7FRT ; 7FRU ; 7KEN ; 7KEY ; 7KLX ; 7L0C ; 7L0H ; 7LFO ; 7MKZ ; 7MM1 ; 7MN7 ; 7MN9 ; 7MNA ; 7MNB ; 7MNC ; 7MND ; 7MNE ; 7MNF ; 7MOU ; 7MOV ; 7MOW ; 7RIN ; 7S4F ; 8DU7 ; 8EXI ; 8EXJ ; 8EXK ; 8EXM ; 8EXN ; 8EYA ; 8EYB ; 8EYC ; 8F88 ; 8G65 ; 8G67 ; 8G68 ; 8G69 ; 8G6A ; 8SKL ; 8U1E
• EC Number: 3.1.3.48
• Pfam ID: PF00102
• Sequence:
  MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLH
  QEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLK
  CAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWP
  DFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKD
  PSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLE
  PPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYG
  IESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLT
  AGAYLCYRFLFNSNT
• Function: Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.
• Tissue Specificity: Expressed in keratinocytes (at protein level).
• KEGG Pathway:
  Adherens junction (hsa04520)
  Insulin sig.ling pathway (hsa04910)
  Insulin resistance (hsa04931)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway:
  Negative regulation of MET activity (R-HSA-6807004)
  Insulin receptor recycling (R-HSA-77387)
  Regulation of IFNG signaling (R-HSA-877312)
  PTK6 Down-Regulation (R-HSA-8849472)
  MECP2 regulates neuronal receptors and channels (R-HSA-9022699)
  Regulation of IFNA/IFNB signaling (R-HSA-912694)
  Growth hormone receptor signaling (R-HSA-982772)
  Integrin signaling (R-HSA-354192)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-nitrophenyl phosphate	DMBX4UJ	Investigative	Tyrosine-protein phosphatase non-receptor type 1 (PTPN1) increases the hydrolysis of 4-nitrophenyl phosphate.	[7]

22 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 Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[6]
Benzoic acid	DMKB9FI	Approved	Benzoic acid decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[7]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[8]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[10]
Trodusquemine	DMQ7UN6	Phase 1	Trodusquemine decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[14]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[15]
acrolein	DMAMCSR	Investigative	acrolein decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[16]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[17]
Morin	DM2OGZ5	Investigative	Morin decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[18]
methylglyoxal	DMRC3OZ	Investigative	methylglyoxal increases the expression of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[19]
1,2-NAPHTHOQUINONE	DMYXELH	Investigative	1,2-NAPHTHOQUINONE decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[20]
Sanggenon C	DMSF5DW	Investigative	Sanggenon C decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[21]
Sanggenon G	DMNHUOD	Investigative	Sanggenon G decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[21]
Kuwanon L	DMX4D1Q	Investigative	Kuwanon L decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[21]
Mulberrofuran C	DMYV49C	Investigative	Mulberrofuran C decreases the activity of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[21]

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 Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tyrosine-protein phosphatase non-receptor type 1 (PTPN1).	[11]

References

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• [2] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [3] 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.
• [4] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling. Neurotoxicology. 2015 Sep;50:56-70.
• [7] Synthesis, biological activity and structure-activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells. Eur J Med Chem. 2014 Jan;71:112-27. doi: 10.1016/j.ejmech.2013.11.001. Epub 2013 Nov 11.
• [8] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [9] 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.
• [10] Coumarins from Angelica decursiva inhibit -glucosidase activity and protein tyrosine phosphatase 1B. Chem Biol Interact. 2016 May 25;252:93-101. doi: 10.1016/j.cbi.2016.04.020. Epub 2016 Apr 13.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring). 2010 Aug;18(8):1516-23.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [15] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [16] Kinetics and mechanism of protein tyrosine phosphatase 1B inactivation by acrolein. Chem Res Toxicol. 2007 Sep;20(9):1315-20. doi: 10.1021/tx700213s. Epub 2007 Jul 27.
• [17] Activation of PTP1B/EGFR signaling and cytotoxicity during combined exposure to ambient electrophiles in A431 cells. J Toxicol Sci. 2021;46(4):177-185. doi: 10.2131/jts.46.177.
• [18] Inhibition of protein tyrosine phosphatase 1B by flavonoids: A structure - activity relationship study. Food Chem Toxicol. 2018 Jan;111:474-481. doi: 10.1016/j.fct.2017.11.039. Epub 2017 Nov 22.
• [19] Resveratrol upregulates Nrf2 expression to attenuate methylglyoxal-induced insulin resistance in Hep G2 cells. J Agric Food Chem. 2012 Sep 12;60(36):9180-7. doi: 10.1021/jf302831d. Epub 2012 Aug 29.
• [20] Activation of EGFR/MEK/ERK/AP-1 signaling mediated by 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary A549 cells. J Toxicol Sci. 2013;38(5):793-7. doi: 10.2131/jts.38.793.
• [21] Protein tyrosine phosphatase 1B inhibitors from Morus root bark. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1426-9.