Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTM4N1J)

• DOT Name: Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1)
• Synonyms: EC 3.1.3.-
• Gene Name: PTPDC1
• UniProt ID: PTPC1_HUMAN
• EC Number: 3.1.3.-
• Pfam ID: PF00782
• Sequence:
  MAAGVLPQNEQPYSTLVNNSECVANMKGNLERPTPKYTKVGERLRHVIPGHMACSMACGG
  RACKYENPARWSEQEQAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIIN
  LQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFYNFGWKDYGVASLTTILDMVKVMTFA
  LQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCVREF
  TQFLTPLRNIFSCCDPKAHAVTLPQYLIRQRHLLHGYEARLLKHVPKIIHLVCKLLLDLA
  ENRPVMMKDVSEGPGLSAEIEKTMSEMVTMQLDKELLRHDSDVSNPPNPTAVAADFDNRG
  MIFSNEQQFDPLWKRRNVECLQPLTHLKRRLSYSDSDLKRAENLLEQGETPQTVPAQILV
  GHKPRQQKLISHCYIPQSPEPDLHKEALVRSTLSFWSQSKFGGLEGLKDNGSPIFHGRII
  PKEAQQSGAFSADVSGSHSPGEPVSPSFANVHKDPNPAHQQVSHCQCKTHGVGSPGSVRQ
  NSRTPRSPLDCGSSPKAQFLVEHETQDSKDLSEAASHSALQSELSAEARRILAAKALANL
  NESVEKEELKRKVEMWQKELNSRDGAWERICGERDPFILCSLMWSWVEQLKEPVITKEDV
  DMLVDRRADAAEALFLLEKGQHQTILCVLHCIVNLQTIPVDVEEAFLAHAIKAFTKVNFD
  SENGPTVYNTLKKIFKHTLEEKRKMTKDGPKPGL
• Function: May play roles in cilia formation and/or maintenance.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein tyrosine phosphatase domain-containing protein 1 (PTPDC1).	[10]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] 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.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.