Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTX09M4)

• DTT Name: Ribonucleotide reductase (RIR)
• Synonyms: Ribonucleoside diphosphate reductase; RIR1
• Gene Name: RIR
• DTT Type: Successful target; [1]
• Related Disease:
  Mature B-cell lymphoma [ICD-11: 2A85]
  Myelodysplastic syndrome [ICD-11: 2A37]
• BioChemical Class: CH/CH(2) oxidoreductase
• UniProt ID: RIR1_HUMAN ; RIR2_HUMAN ; RIR2B_HUMAN
• TTD ID: T73342
• Sequence:
  MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLA
  AETAATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMEDLYNYINPHNGKHSPMVAKST
  LDIVLANKDRLNSAIIYDRDFSYNYFGFKTLERSYLLKINGKVAERPQHMLMRVSVGIHK
  EDIDAAIETYNLLSERWFTHASPTLFNAGTNRPQLSSCFLLSMKDDSIEGIYDTLKQCAL
  ISKSAGGIGVAVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNKRPGAFAIY
  LEPWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMCPNECPGLD
  EVWGEEFEKLYASYEKQGRVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNL
  GTIKCSNLCTEIVEYTSKDEVAVCNLASLALNMYVTSEHTYDFKKLAEVTKVVVRNLNKI
  IDINYYPVPEACLSNKRHRPIGIGVQGLADAFILMRYPFESAEAQLLNKQIFETIYYGAL
  EASCDLAKEQGPYETYEGSPVSKGILQYDMWNVTPTDLWDWKVLKEKIAKYGIRNSLLIA
  PMPTASTAQILGNNESIEPYTSNIYTRRVLSGEFQIVNPHLLKDLTERGLWHEEMKNQII
  ACNGSIQSIPEIPDDLKQLYKTVWEISQKTVLKMAAERGAFIDQSQSLNIHIAEPNYGKL
  TSMHFYGWKQGLKTGMYYLRTRPAANPIQFTLNKEKLKDKEKVSKEEEEKERNTAAMVCS
  LENRDECLMCGS
• Function: Ribonucleoside-diphosphate reductase holoenzyme provides the precursors necessary for viral DNA synthesis. Allows virus growth in non-dividing cells, as well as reactivation from latency in infected hosts. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. The N-terminal region confers antiapoptotic activity in differentiated cells such as neurons and is importantfor viral reactivation to increase neural survivability.
• 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-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clofarabine	DMCVJ86	Acute lymphoblastic leukaemia	2A85	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CPX-POM	DMK7DFM	Bladder cancer	2C94	Phase 2	[2]
G-207 virus construct	DM32AKH	Glioma	2A00.0	Phase 1/2	[3], [4]
COH29	DMMEFO0	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Didox	DM64CAS	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[6]
Amidox	DM3D0WA	N. A.	N. A.	Terminated	[8]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trimidox	DMY8GDA	Solid tumour/cancer	2A00-2F9Z	Preclinical	[7]

References

• [1] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [2] Preclinical Pharmacokinetics of Fosciclopirox, a Novel Treatment of Urothelial Cancers, in Rats and Dogs. J Pharmacol Exp Ther. 2019 Aug;370(2):148-159.
• [3] Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma. Chin J Cancer. 2011 Dec;30(12):831-41.
• [4] Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal metastases. Ann Surg. 2004 Jun;239(6):892-9; discussion 899-902.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Didox (a novel ribonucleotide reductase inhibitor) overcomes Bcl-2 mediated radiation resistance in prostate cancer cell line PC-3. Cancer Biol Ther. 2002 Sep-Oct;1(5):539-45.
• [7] Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox: novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea. Antiviral Res. 2002 Nov;56(2):167-81.
• [8] Metabolism of the new ribonucleotide reductase inhibitor amidox in the isolated perfused rat liver. Anticancer Res. 2000 Sep- Oct;20(5B):3521-6.