Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8GBUR)

• DOT Name: Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B)
• Synonyms: EC 1.17.4.1; TP53-inducible ribonucleotide reductase M2 B; p53-inducible ribonucleotide reductase small subunit 2-like protein; p53R2
• Gene Name: RRM2B
• Related Disease:
  Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1
  Acute liver failure
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Anal intraepithelial neoplasia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Childhood myelodysplastic syndrome
  Cholangiocarcinoma
  Colorectal carcinoma
  Fatty liver disease
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Intellectual disability
  Lactic acidosis
  Mitochondrial disease
  Mitochondrial DNA depletion syndrome
  Mitochondrial DNA depletion syndrome 8a
  Mitochondrial myopathy
  Myelodysplastic syndrome
  Nephropathy
  Osteoarthritis
  Progressive external ophthalmoplegia
  Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5
  Transitional cell carcinoma
  Ulcerative colitis
  Urothelial carcinoma
  Inclusion body myositis
  Melanoma
  Prostate cancer
  Prostate carcinoma
  Status epilepticus seizure
  Adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy
  Autosomal dominant progressive external ophthalmoplegia
  Kearns-Sayre syndrome
  Mitochondrial neurogastrointestinal encephalomyopathy
  Neuroblastoma
  Colorectal adenoma
  Esophageal squamous cell carcinoma
  Nasopharyngeal carcinoma
  Oropharyngeal carcinoma
  Pachyonychia congenita 3
  Peripheral sensory neuropathies
  Squamous cell carcinoma
• UniProt ID: RIR2B_HUMAN
• PDB ID: 2VUX; 3HF1; 4DJN
• EC Number: 1.17.4.1
• Pfam ID: PF00268
• Sequence:
  MGDPERPEAAGLDQDERSSSDTNESEIKSNEEPLLRKSSRRFVIFPIQYPDIWKMYKQAQ
  ASFWTAEEVDLSKDLPHWNKLKADEKYFISHILAFFAASDGIVNENLVERFSQEVQVPEA
  RCFYGFQILIENVHSEMYSLLIDTYIRDPKKREFLFNAIETMPYVKKKADWALRWIADRK
  STFGERVVAFAAVEGVFFSGSFAAIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFQ
  YLVNKPSEERVREIIVDAVKIEQEFLTEALPVGLIGMNCILMKQYIEFVADRLLVELGFS
  KVFQAENPFDFMENISLEGKTNFFEKRVSEYQRFAVMAETTDNVFTLDADF
• Function: Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage.
• Tissue Specificity: Widely expressed at a high level in skeletal muscle and at a weak level in thymus. Expressed in epithelial dysplasias and squamous cell carcinoma.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Glutathione metabolism (hsa00480)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  p53 sig.ling pathway (hsa04115)
• Reactome Pathway:
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Interconversion of nucleotide di- and triphosphates (R-HSA-499943)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1	DIS9NLHF	Definitive	GermlineCausalMutation	[1]
Acute liver failure	DIS5EZKX	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[2]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[12]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[12]
Intellectual disability	DISMBNXP	Strong	Biomarker	[13]
Lactic acidosis	DISZI1ZK	Strong	Biomarker	[14]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[15]
Mitochondrial DNA depletion syndrome	DISIGZSM	Strong	Genetic Variation	[16]
Mitochondrial DNA depletion syndrome 8a	DISTUBAP	Strong	Autosomal recessive	[17]
Mitochondrial myopathy	DIS9SA7V	Strong	Biomarker	[14]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[3]
Nephropathy	DISXWP4P	Strong	Biomarker	[14]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[18]
Progressive external ophthalmoplegia	DISX4ATI	Strong	Genetic Variation	[19]
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5	DISU350O	Strong	Autosomal dominant	[20]
Transitional cell carcinoma	DISWVVDR	Strong	Genetic Variation	[21]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[22]
Urothelial carcinoma	DISRTNTN	Strong	Genetic Variation	[21]
Inclusion body myositis	DISZXXG5	moderate	Genetic Variation	[23]
Melanoma	DIS1RRCY	moderate	Biomarker	[24]
Prostate cancer	DISF190Y	moderate	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[25]
Status epilepticus seizure	DISY3BIC	moderate	Biomarker	[26]
Adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy	DISUXRUM	Supportive	Autosomal dominant	[27]
Autosomal dominant progressive external ophthalmoplegia	DISXBSXA	Supportive	Autosomal dominant	[1]
Kearns-Sayre syndrome	DIS9UK5R	Supportive	Autosomal recessive	[13]
Mitochondrial neurogastrointestinal encephalomyopathy	DIS5HV4H	Supportive	Autosomal recessive	[28]
Neuroblastoma	DISVZBI4	Disputed	Biomarker	[29]
Colorectal adenoma	DISTSVHM	Limited	Genetic Variation	[30]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Biomarker	[31]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[32]
Oropharyngeal carcinoma	DIS7K3AI	Limited	Biomarker	[33]
Pachyonychia congenita 3	DISZLC6C	Limited	Biomarker	[34]
Peripheral sensory neuropathies	DISYWI6M	Limited	Biomarker	[35]
Squamous cell carcinoma	DISQVIFL	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[41]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[42]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[43]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[48]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[49]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[50]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[51]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[3]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[40]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[40]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[40]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[52]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[40]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[53]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[54]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[55]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[50]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[58]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[59]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[39]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B).	[41]

References

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