Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8ZAK8)

• DOT Name: Peroxiredoxin-like 2C (PRXL2C)
• Synonyms: AhpC/TSA antioxidant enzyme domain-containing protein 1; Thioredoxin-like protein AAED1
• Gene Name: PRXL2C
• Related Disease:
  Advanced cancer
  Attention deficit hyperactivity disorder
  Gastric cancer
  Stomach cancer
• UniProt ID: PXL2C_HUMAN
• Pfam ID: PF13911
• Sequence:
  MAAPAPVTRQVSGAAALVPAPSGPDSGQPLAAAVAELPVLDARGQRVPFGALFRERRAVV
  VFVRHFLCYICKEYVEDLAKIPRSFLQEANVTLIVIGQSSYHHIEPFCKLTGYSHEIYVD
  PEREIYKRLGMKRGEEIASSGQSPHIKSNLLSGSLQSLWRAVTGPLFDFQGDPAQQGGTL
  ILGPGNNIHFIHRDRNRLDHKPINSVLQLVGVQHVNFTNRPSVIHV
• Function: May positively regulate ERK1/2 signaling and AKT1 activation leading to HIF1A up-regulation with an increased expression of glycolysis genes and enhanced glycolysis.
• Tissue Specificity: Expressed in gastric tissues.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]

6 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 Peroxiredoxin-like 2C (PRXL2C).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Peroxiredoxin-like 2C (PRXL2C).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Peroxiredoxin-like 2C (PRXL2C).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Peroxiredoxin-like 2C (PRXL2C).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Peroxiredoxin-like 2C (PRXL2C).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Peroxiredoxin-like 2C (PRXL2C).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Peroxiredoxin-like 2C (PRXL2C).	[8]

References

• [1] AAED1 modulates proliferation and glycolysis in gastric cancer.Oncol Rep. 2018 Aug;40(2):1156-1164. doi: 10.3892/or.2018.6478. Epub 2018 Jun 7.
• [2] Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing.Mol Psychiatry. 2020 Sep;25(9):2047-2057. doi: 10.1038/s41380-018-0210-6. Epub 2018 Aug 16.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [8] 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.