Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJUQ122)

• DOT Name: PEST proteolytic signal-containing nuclear protein (PCNP)
• Synonyms: PCNP; PEST-containing nuclear protein
• Gene Name: PCNP
• Related Disease:
  Neoplasm
  Advanced cancer
  B-cell neoplasm
  Lung adenocarcinoma
  Neuroblastoma
  Rheumatoid arthritis
• UniProt ID: PCNP_HUMAN
• Pfam ID: PF15473
• Sequence:
  MADGKAGDEKPEKSQRAGAAGGPEEEAEKPVKTKTVSSSNGGESSSRSAEKRSAEEEAAD
  LPTKPTKISKFGFAIGSQTTKKASAISIKLGSSKPKETVPTLAPKTLSVAAAFNEDEDSE
  PEEMPPEAKMRMKNIGRDTPTSAGPNSFNKGKHGFSDNQKLWERNIKSHLGNVHDQDN
• Function: May be involved in cell cycle regulation.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Disputed	Biomarker	[4]

13 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 PEST proteolytic signal-containing nuclear protein (PCNP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[10]
Aspirin	DM672AH	Approved	Aspirin increases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[11]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[12]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of PEST proteolytic signal-containing nuclear protein (PCNP).	[17]

2 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 PEST proteolytic signal-containing nuclear protein (PCNP).	[14]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of PEST proteolytic signal-containing nuclear protein (PCNP).	[18]

References

• [1] PEST-containing nuclear protein regulates cell proliferation, migration, and invasion in lung adenocarcinoma.Oncogenesis. 2019 Mar 14;8(3):22. doi: 10.1038/s41389-019-0132-4.
• [2] Taking a holistic view of PEST-containing nuclear protein (PCNP) in cancer biology.Cancer Med. 2019 Oct;8(14):6335-6343. doi: 10.1002/cam4.2465. Epub 2019 Sep 5.
• [3] PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways.BMC Cancer. 2018 May 2;18(1):499. doi: 10.1186/s12885-018-4391-9.
• [4] TIPE2 expression is increased in peripheral blood mononuclear cells from patients with rheumatoid arthritis.Oncotarget. 2017 Sep 23;8(50):87472-87479. doi: 10.18632/oncotarget.21267. eCollection 2017 Oct 20.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [12] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [13] 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.
• [14] 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.
• [15] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [18] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.