Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXGQOR9)

• DOT Name: Ribonucleoside-diphosphate reductase large subunit (RRM1)
• Synonyms: EC 1.17.4.1; Ribonucleoside-diphosphate reductase subunit M1; Ribonucleotide reductase large subunit
• Gene Name: RRM1
• UniProt ID: RIR1_HUMAN
• PDB ID: 2WGH; 3HNC; 3HND; 3HNE; 3HNF; 4X3V; 5D1Y; 5TUS; 6AUI; 6L3R; 6L7L; 6LKM
• EC Number: 1.17.4.1
• Pfam ID: PF03477 ; PF02867 ; PF00317
• Sequence:
  MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLA
  AETAATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMEDLYNYINPHNGKHSPMVAKST
  LDIVLANKDRLNSAIIYDRDFSYNYFGFKTLERSYLLKINGKVAERPQHMLMRVSVGIHK
  EDIDAAIETYNLLSERWFTHASPTLFNAGTNRPQLSSCFLLSMKDDSIEGIYDTLKQCAL
  ISKSAGGIGVAVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNKRPGAFAIY
  LEPWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMCPNECPGLD
  EVWGEEFEKLYASYEKQGRVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNL
  GTIKCSNLCTEIVEYTSKDEVAVCNLASLALNMYVTSEHTYDFKKLAEVTKVVVRNLNKI
  IDINYYPVPEACLSNKRHRPIGIGVQGLADAFILMRYPFESAEAQLLNKQIFETIYYGAL
  EASCDLAKEQGPYETYEGSPVSKGILQYDMWNVTPTDLWDWKVLKEKIAKYGIRNSLLIA
  PMPTASTAQILGNNESIEPYTSNIYTRRVLSGEFQIVNPHLLKDLTERGLWHEEMKNQII
  ACNGSIQSIPEIPDDLKQLYKTVWEISQKTVLKMAAERGAFIDQSQSLNIHIAEPNYGKL
  TSMHFYGWKQGLKTGMYYLRTRPAANPIQFTLNKEKLKDKEKVSKEEEEKERNTAAMVCS
  LENRDECLMCGS
• Function: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Glutathione metabolism (hsa00480)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway: Interconversion of nucleotide di- and triphosphates (R-HSA-499943)
• BioCyc Pathway: MetaCyc:HS09541-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gemcitabine	DMSE3I7	Approved	Ribonucleoside-diphosphate reductase large subunit (RRM1) affects the response to substance of Gemcitabine.	[28]
Gefitinib	DM15F0X	Approved	Ribonucleoside-diphosphate reductase large subunit (RRM1) affects the response to substance of Gefitinib.	[29]
Fialuridine	DMCIGRB	Phase 2	Ribonucleoside-diphosphate reductase large subunit (RRM1) affects the response to substance of Fialuridine.	[30]

29 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 Ribonucleoside-diphosphate reductase large subunit (RRM1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[14]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[15]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[16]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[17]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[18]
Mitotane	DMU1GX0	Approved	Mitotane increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[20]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Ribonucleoside-diphosphate reductase large subunit (RRM1).	[24]

References

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