Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIVZ5LL)

• DOT Name: Pleiotropic regulator 1 (PLRG1)
• Gene Name: PLRG1
• Related Disease:
  Esophageal squamous cell carcinoma
  Liver failure
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Hepatocellular carcinoma
  Castration-resistant prostate carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PLRG1_HUMAN
• PDB ID: 4YVD; 5MQF; 5XJC; 5YZG; 5Z56; 5Z57; 5Z58; 6FF4; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6ZYM; 7AAV; 7ABF; 7ABG; 7ABI; 7DH6; 7DVQ; 7QTT; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF00400
• Sequence:
  MVEEVQKHSVHTLVFRSLKRTHDMFVADNGKPVPLDEESHKRKMAIKLRNEYGPVLHMPT
  SKENLKEKGPQNATDSYVHKQYPANQGQEVEYFVAGTHPYPPGPGVALTADTKIQRMPSE
  SAAQSLAVALPLQTKADANRTAPSGSEYRHPGASDRPQPTAMNSIVMETGNTKNSALMAK
  KAPTMPKPQWHPPWKLYRVISGHLGWVRCIAVEPGNQWFVTGSADRTIKIWDLASGKLKL
  SLTGHISTVRGVIVSTRSPYLFSCGEDKQVKCWDLEYNKVIRHYHGHLSAVYGLDLHPTI
  DVLVTCSRDSTARIWDVRTKASVHTLSGHTNAVATVRCQAAEPQIITGSHDTTIRLWDLV
  AGKTRVTLTNHKKSVRAVVLHPRHYTFASGSPDNIKQWKFPDGSFIQNLSGHNAIINTLT
  VNSDGVLVSGADNGTMHLWDWRTGYNFQRVHAAVQPGSLDSESGIFACAFDQSESRLLTA
  EADKTIKVYREDDTATEETHPVSWKPEIIKRKRF
• Function: Involved in pre-mRNA splicing as component of the spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[1]
Liver failure	DISLGEL6	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[6]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[7]
Prostate cancer	DISF190Y	Limited	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pleiotropic regulator 1 (PLRG1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pleiotropic regulator 1 (PLRG1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pleiotropic regulator 1 (PLRG1).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Pleiotropic regulator 1 (PLRG1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pleiotropic regulator 1 (PLRG1).	[13]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Pleiotropic regulator 1 (PLRG1).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Pleiotropic regulator 1 (PLRG1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Pleiotropic regulator 1 (PLRG1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pleiotropic regulator 1 (PLRG1).	[11]

References

• [1] Expression of phosphatase of regenerating liver 1 and 3 mRNA in esophageal squamous cell carcinoma.Arch Pathol Lab Med. 2008 Aug;132(8):1307-12. doi: 10.5858/2008-132-1307-EOPORL.
• [2] Dynamic Regulation of miRNA Expression by Functionally Enhanced Placental Mesenchymal Stem Cells PromotesHepatic Regeneration in a Rat Model with Bile Duct Ligation.Int J Mol Sci. 2019 Oct 24;20(21):5299. doi: 10.3390/ijms20215299.
• [3] miR-339-5p Increases Radiosensitivity of Lung Cancer Cells by Targeting Phosphatases of Regenerating Liver-1 (PRL-1).Med Sci Monit. 2018 Nov 21;24:8408-8416. doi: 10.12659/MSM.910808.
• [4] Oncogenic function and prognostic significance of protein tyrosine phosphatase PRL-1 in hepatocellular carcinoma.Oncotarget. 2014 Jun 15;5(11):3685-96. doi: 10.18632/oncotarget.1986.
• [5] MicroRNA-26a inhibits cell proliferation and invasion of cervical cancer cells by targeting protein tyrosine phosphatase type IVA 1.Mol Med Rep. 2014 Sep;10(3):1426-32. doi: 10.3892/mmr.2014.2335. Epub 2014 Jun 16.
• [6] Exploring the cause of the inhibitor 4AX attaching to binding site disrupting protein tyrosine phosphatase 4A1 trimerization by molecular dynamic simulation.J Biomol Struct Dyn. 2019 Nov;37(18):4840-4851. doi: 10.1080/07391102.2019.1567392. Epub 2019 Jan 31.
• [7] Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method.Urol Oncol. 2014 Aug;32(6):769-78. doi: 10.1016/j.urolonc.2014.03.007. Epub 2014 Jun 23.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.