Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ZMFZE)

• DOT Name: p53 and DNA damage-regulated protein 1 (PDRG1)
• Gene Name: PDRG1
• Related Disease:
  Advanced cancer
  Bladder cancer
  Colon cancer
  Liver cancer
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Stomach cancer
• UniProt ID: PDRG1_HUMAN
• Pfam ID: PF01920
• Sequence:
  MLSPEAERVLRYLVEVEELAEEVLADKRQIVDLDTKRNQNREGLRALQKDLSLSEDVMVC
  FGNMFIKMPHPETKEMIEKDQDHLDKEIEKLRKQLKVKVNRLFEAQGKPELKGFNLNPLN
  QDELKALKVILKG
• Function: May play a role in chaperone-mediated protein folding.
• Tissue Specificity: Predominantly expressed in normal testis and exhibits reduced but detectable expression in other organs.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[4]
Lung cancer	DISCM4YA	Limited	Biomarker	[5]
Lung carcinoma	DISTR26C	Limited	Biomarker	[5]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[4]

8 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 p53 and DNA damage-regulated protein 1 (PDRG1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of p53 and DNA damage-regulated protein 1 (PDRG1).	[14]

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 decreases the methylation of p53 and DNA damage-regulated protein 1 (PDRG1).	[12]

References

• [1] PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress.Cancer Biol Ther. 2011 Mar 15;11(6):567-73. doi: 10.4161/cbt.11.6.14412. Epub 2011 Mar 15.
• [2] MicroRNA-214 suppresses oncogenesis and exerts impact on prognosis by targeting PDRG1 in bladder cancer.PLoS One. 2015 Feb 23;10(2):e0118086. doi: 10.1371/journal.pone.0118086. eCollection 2015.
• [3] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [4] PDRG1 gene silencing contributes to inhibit the growth and induce apoptosis of gastric cancer cells.Pathol Res Pract. 2019 Oct;215(10):152567. doi: 10.1016/j.prp.2019.152567. Epub 2019 Jul 27.
• [5] The PDRG1 is an oncogene in lung cancer cells, promoting radioresistance via the ATM-P53 signaling pathway.Biomed Pharmacother. 2016 Oct;83:1471-1477. doi: 10.1016/j.biopha.2016.08.034. Epub 2016 Sep 7.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.