Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZSES3W)

• DOT Name: Oxidized purine nucleoside triphosphate hydrolase (NUDT1)
• Synonyms: EC 3.6.1.56; 2-hydroxy-dATP diphosphatase; 7,8-dihydro-8-oxoguanine triphosphatase; 8-oxo-dGTPase; Methylated purine nucleoside triphosphate hydrolase; EC 3.6.1.-; Nucleoside diphosphate-linked moiety X motif 1; Nudix motif 1
• Gene Name: NUDT1
• Related Disease:
  Adenoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Colon cancer
  Colon carcinoma
  Congenital contractural arachnodactyly
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Familial adenomatous polyposis
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate neoplasm
  Squamous cell carcinoma
  Ulcerative colitis
  Bladder cancer
  Myocardial ischemia
  Plasma cell myeloma
  Small-cell lung cancer
  Type-1 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bone osteosarcoma
  High blood pressure
  Osteosarcoma
  Amyotrophic lateral sclerosis
  Coronary atherosclerosis
  Cryohydrocytosis
  Epstein barr virus infection
  Gastric cancer
  Hashimoto thyroiditis
  Matthew-Wood syndrome
  Melanoma
  Neuroendocrine neoplasm
  Pancreatic ductal carcinoma
  Stomach cancer
• UniProt ID: 8ODP_HUMAN
• PDB ID: 1IRY ; 3Q93 ; 3WHW ; 3ZR0 ; 3ZR1 ; 4C9W ; 4C9X ; 4N1T ; 4N1U ; 5ANS ; 5ANT ; 5ANU ; 5ANV ; 5ANW ; 5FSI ; 5FSK ; 5FSL ; 5FSM ; 5FSN ; 5FSO ; 5GHI ; 5GHJ ; 5GHM ; 5GHN ; 5GHO ; 5GHP ; 5GHQ ; 5NGR ; 5NGS ; 5NGT ; 5NHY ; 5OTM ; 5WS7 ; 6AA3 ; 6AA4 ; 6AA5 ; 6EQ2 ; 6EQ3 ; 6EQ4 ; 6EQ5 ; 6EQ6 ; 6EQ7 ; 6F1X ; 6F20 ; 6F22 ; 6F23 ; 6GLE ; 6GLF ; 6GLG ; 6GLH ; 6GLI ; 6GLJ ; 6GLK ; 6GLL ; 6GLM ; 6GLN ; 6GLO ; 6GLP ; 6GLQ ; 6GLR ; 6GLS ; 6GLT ; 6GLU ; 6GLV ; 6IJY ; 6ILI ; 6IMZ ; 6JVF ; 6JVG ; 6JVH ; 6JVI ; 6JVJ ; 6JVK ; 6JVL ; 6JVM ; 6JVN ; 6JVO ; 6JVP ; 6JVQ ; 6JVR ; 6JVS ; 6JVT ; 6QVO ; 6US2 ; 6US3 ; 6US4 ; 7ESF ; 7N03 ; 7N13 ; 8A07 ; 8A0S ; 8A0T ; 8A34 ; 8A3A ; 8I18 ; 8I19 ; 8I1A ; 8I1C ; 8I1D ; 8I1E ; 8I1F ; 8I1G ; 8I1H ; 8I1I ; 8I1J ; 8I8S ; 8I8T
• EC Number: 3.6.1.-; 3.6.1.56
• Pfam ID: PF00293
• Sequence:
  MGASRLYTLVLVLQPQRVLLGMKKRGFGAGRWNGFGGKVQEGETIEDGARRELQEESGLT
  VDALHKVGQIVFEFVGEPELMDVHVFCTDSIQGTPVESDEMRPCWFQLDQIPFKDMWPDD
  SYWFPLLLQKKKFHGYFKFQGQDTILDYTLREVDTV
• Function: Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool. Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP. Has also a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP. Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A. Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA. Through this antimutagenic activity protects cells from oxidative stress.
• Tissue Specificity: Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes.
• Reactome Pathway: Phosphate bond hydrolysis by NUDT proteins (R-HSA-2393930)
• BioCyc Pathway: MetaCyc:HS02879-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Colon cancer	DISVC52G	Strong	Genetic Variation	[8]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[8]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[11]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[14]
Lung cancer	DISCM4YA	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[15]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[18]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[17]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[19]
Bladder cancer	DISUHNM0	moderate	Biomarker	[20]
Myocardial ischemia	DISFTVXF	moderate	Genetic Variation	[21]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[22]
Small-cell lung cancer	DISK3LZD	moderate	Genetic Variation	[23]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[24]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[20]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[20]
Bone osteosarcoma	DIST1004	Disputed	Altered Expression	[25]
High blood pressure	DISY2OHH	Disputed	Biomarker	[26]
Osteosarcoma	DISLQ7E2	Disputed	Altered Expression	[25]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Altered Expression	[27]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[21]
Cryohydrocytosis	DISMQHL3	Limited	Genetic Variation	[28]
Epstein barr virus infection	DISOO0WT	Limited	Altered Expression	[29]
Gastric cancer	DISXGOUK	Limited	Biomarker	[30]
Hashimoto thyroiditis	DIS77CDF	Limited	Biomarker	[31]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[32]
Melanoma	DIS1RRCY	Limited	Altered Expression	[33]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[34]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[32]
Stomach cancer	DISKIJSX	Limited	Biomarker	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Oxidized purine nucleoside triphosphate hydrolase (NUDT1) increases the response to substance of Hydrogen peroxide.	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[35]

18 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 Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[42]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[43]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[45]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[47]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[50]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[41]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Oxidized purine nucleoside triphosphate hydrolase (NUDT1).	[51]

References

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