Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXI2NTI)

• DOT Name: Glutathione peroxidase 2 (GPX2)
• Synonyms: GPx-2; GSHPx-2; EC 1.11.1.9; Gastrointestinal glutathione peroxidase; Glutathione peroxidase-gastrointestinal; GPx-GI; GSHPx-GI; Glutathione peroxidase-related protein 2; GPRP-2; Phospholipid hydroperoxide glutathione peroxidase GPX2; EC 1.11.1.12
• Gene Name: GPX2
• Related Disease:
  Lung squamous cell carcinoma
  Prostate cancer
  Prostate carcinoma
  Adenoma
  Breast neoplasm
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Colonic neoplasm
  Colorectal adenoma
  Colorectal neoplasm
  Hepatocellular carcinoma
  Intestinal cancer
  Liver cancer
  Lung cancer
  Lung carcinoma
  Rectal carcinoma
  Stomach cancer
  Transitional cell carcinoma
  Ulcerative colitis
  Urothelial carcinoma
  Advanced cancer
  Bladder cancer
  Lung adenocarcinoma
  Neoplasm
  Pancreatic cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  46,XY sex reversal 2
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Charcot-Marie-Tooth disease type 3
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Hepatitis C virus infection
  Inflammatory bowel disease
  Nasopharyngeal carcinoma
• UniProt ID: GPX2_HUMAN
• PDB ID: 2HE3
• EC Number: 1.11.1.12; 1.11.1.9
• Pfam ID: PF00255
• Sequence:
  MAFIAKSFYDLSAISLDGEKVDFNTFRGRAVLIENVASLUGTTTRDFTQLNELQCRFPRR
  LVVLGFPCNQFGHQENCQNEEILNSLKYVRPGGGYQPTFTLVQKCEVNGQNEHPVFAYLK
  DKLPYPYDDPFSLMTDPKLIIWSPVRRSDVAWNFEKFLIGPEGEPFRRYSRTFPTINIEP
  DIKRLLKVAI
• Function: Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis. Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides. Cannot reduce phosphatidycholine hydroperoxide.
• Tissue Specificity: Mostly in liver and gastrointestinal tract, not found in heart or kidney.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Thyroid hormone synthesis (hsa04918)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Synthesis of 12-eicosatetraenoic acid derivatives (R-HSA-2142712)
  Synthesis of 15-eicosatetraenoic acid derivatives (R-HSA-2142770)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Synthesis of 5-eicosatetraenoic acids (R-HSA-2142688)
• BioCyc Pathway: MetaCyc:HS11006-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung squamous cell carcinoma	DISXPIBD	Definitive	Altered Expression	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[7]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Intestinal cancer	DISYCNF1	Strong	Biomarker	[10]
Liver cancer	DISDE4BI	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Rectal carcinoma	DIS8FRR7	Strong	Genetic Variation	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[14]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[15]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[16]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[15]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[1]
Bladder cancer	DISUHNM0	moderate	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[6]
Neoplasm	DISZKGEW	moderate	Altered Expression	[14]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[17]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[15]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[15]
46,XY sex reversal 2	DIS0USUN	Limited	Altered Expression	[18]
Breast cancer	DIS7DPX1	Limited	Biomarker	[19]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[19]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[2]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Altered Expression	[18]
Colitis	DISAF7DD	Limited	Biomarker	[20]
Colon cancer	DISVC52G	Limited	Altered Expression	[21]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[21]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[22]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[23]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Glutathione peroxidase 2 (GPX2) affects the response to substance of Methotrexate.	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glutathione peroxidase 2 (GPX2).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione peroxidase 2 (GPX2).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glutathione peroxidase 2 (GPX2).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glutathione peroxidase 2 (GPX2).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutathione peroxidase 2 (GPX2).	[28]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glutathione peroxidase 2 (GPX2).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Glutathione peroxidase 2 (GPX2).	[29]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glutathione peroxidase 2 (GPX2).	[30]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Glutathione peroxidase 2 (GPX2).	[31]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Glutathione peroxidase 2 (GPX2).	[32]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Glutathione peroxidase 2 (GPX2).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glutathione peroxidase 2 (GPX2).	[33]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Glutathione peroxidase 2 (GPX2).	[34]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Glutathione peroxidase 2 (GPX2).	[31]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Glutathione peroxidase 2 (GPX2).	[35]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Glutathione peroxidase 2 (GPX2).	[36]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Glutathione peroxidase 2 (GPX2).	[37]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Glutathione peroxidase 2 (GPX2).	[38]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Glutathione peroxidase 2 (GPX2).	[39]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Glutathione peroxidase 2 (GPX2).	[33]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Glutathione peroxidase 2 (GPX2).	[40]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Glutathione peroxidase 2 (GPX2).	[36]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Glutathione peroxidase 2 (GPX2).	[41]
Atazanavir	DMSYRBX	Approved	Atazanavir decreases the expression of Glutathione peroxidase 2 (GPX2).	[41]
Clavulanate	DM2FGRT	Approved	Clavulanate increases the expression of Glutathione peroxidase 2 (GPX2).	[42]
Mercaptopurine	DMTM2IK	Approved	Mercaptopurine increases the expression of Glutathione peroxidase 2 (GPX2).	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Glutathione peroxidase 2 (GPX2).	[43]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Glutathione peroxidase 2 (GPX2).	[36]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl affects the expression of Glutathione peroxidase 2 (GPX2).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glutathione peroxidase 2 (GPX2).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Glutathione peroxidase 2 (GPX2).	[46]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Glutathione peroxidase 2 (GPX2).	[47]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Glutathione peroxidase 2 (GPX2).	[48]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Glutathione peroxidase 2 (GPX2).	[49]

References

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