Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS8KC8A)

• DOT Name: Peroxiredoxin-6 (PRDX6)
• Synonyms: EC 1.11.1.27; 1-Cys peroxiredoxin; 1-Cys PRX; 24 kDa protein; Acidic calcium-independent phospholipase A2; aiPLA2; EC 3.1.1.4; Antioxidant protein 2; Glutathione-dependent peroxiredoxin; Liver 2D page spot 40; Lysophosphatidylcholine acyltransferase 5; LPC acyltransferase 5; LPCAT-5; Lyso-PC acyltransferase 5; EC 2.3.1.23; Non-selenium glutathione peroxidase; NSGPx; Red blood cells page spot 12
• Gene Name: PRDX6
• Related Disease:
  Hyperglycemia
  Type-1/2 diabetes
  Advanced cancer
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cataract
  Cholangiocarcinoma
  Colitis
  Colorectal adenoma
  Colorectal carcinoma
  Crohn disease
  Esophageal squamous cell carcinoma
  Familial amyotrophic lateral sclerosis
  Fanconi anemia complementation group A
  Fanconi's anemia
  Lung neoplasm
  Male infertility
  Myocardial ischemia
  Neoplasm
  Pick disease
  Stroke
  Thrombocytopenia
  Vitiligo
  Alzheimer disease
  Lung carcinoma
  Pancreatic cancer
  Schizophrenia
  Arthritis
  Rheumatoid arthritis
  Adult respiratory distress syndrome
  Carcinoma
  Contact dermatitis
  Cutaneous melanoma
  Cystitis
  Glaucoma/ocular hypertension
  Hepatocellular carcinoma
  Lung cancer
  Melanoma
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Thyroid gland papillary carcinoma
• UniProt ID: PRDX6_HUMAN
• PDB ID: 1PRX; 5B6M; 5B6N
• EC Number: 1.11.1.27; 2.3.1.23; 3.1.1.4
• Pfam ID: PF10417 ; PF00578
• Sequence:
  MPGGLLLGDVAPNFEANTTVGRIRFHDFLGDSWGILFSHPRDFTPVCTTELGRAAKLAPE
  FAKRNVKLIALSIDSVEDHLAWSKDINAYNCEEPTEKLPFPIIDDRNRELAILLGMLDPA
  EKDEKGMPVTARVVFVFGPDKKLKLSILYPATTGRNFDEILRVVISLQLTAEKRVATPVD
  WKDGDSVMVLPTIPEEEAKKLFPKGVFTKELPSGKKYLRYTPQP
• Function: Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH. Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis. Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
• BioCyc Pathway: MetaCyc:HS04152-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Cataract	DISUD7SL	Strong	Altered Expression	[1]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[10]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[11]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[12]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[12]
Lung neoplasm	DISVARNB	Strong	Biomarker	[13]
Male infertility	DISY3YZZ	Strong	Biomarker	[14]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Pick disease	DISP6X50	Strong	Altered Expression	[17]
Stroke	DISX6UHX	Strong	Altered Expression	[18]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[19]
Vitiligo	DISR05SL	Strong	Altered Expression	[20]
Alzheimer disease	DISF8S70	moderate	Altered Expression	[21]
Lung carcinoma	DISTR26C	moderate	Biomarker	[22]
Pancreatic cancer	DISJC981	moderate	Biomarker	[23]
Schizophrenia	DISSRV2N	moderate	Biomarker	[24]
Arthritis	DIST1YEL	Disputed	Biomarker	[25]
Rheumatoid arthritis	DISTSB4J	Disputed	Altered Expression	[25]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[26]
Carcinoma	DISH9F1N	Limited	Altered Expression	[27]
Contact dermatitis	DISQ3AU0	Limited	Biomarker	[28]
Cutaneous melanoma	DIS3MMH9	Limited	Genetic Variation	[29]
Cystitis	DIS2D4B9	Limited	Biomarker	[30]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Altered Expression	[31]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[32]
Lung cancer	DISCM4YA	Limited	Biomarker	[22]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[29]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[16]
Prostate cancer	DISF190Y	Limited	Altered Expression	[33]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[33]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[27]

18 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-6 (PRDX6).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peroxiredoxin-6 (PRDX6).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Peroxiredoxin-6 (PRDX6).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peroxiredoxin-6 (PRDX6).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Peroxiredoxin-6 (PRDX6).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Peroxiredoxin-6 (PRDX6).	[39]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Peroxiredoxin-6 (PRDX6).	[40]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Peroxiredoxin-6 (PRDX6).	[42]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Peroxiredoxin-6 (PRDX6).	[43]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Peroxiredoxin-6 (PRDX6).	[44]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Peroxiredoxin-6 (PRDX6).	[45]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Peroxiredoxin-6 (PRDX6).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Peroxiredoxin-6 (PRDX6).	[47]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Peroxiredoxin-6 (PRDX6).	[49]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of Peroxiredoxin-6 (PRDX6).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peroxiredoxin-6 (PRDX6).	[51]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Peroxiredoxin-6 (PRDX6).	[52]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Peroxiredoxin-6 (PRDX6).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Peroxiredoxin-6 (PRDX6).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peroxiredoxin-6 (PRDX6).	[48]

References

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