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]
BioChemical Class
CH/CH(2) oxidoreductase
UniProt ID
RIR1_HUMAN ; RIR2_HUMAN ; RIR2B_HUMAN
TTD ID
T73342
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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]
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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]
COH29 DMMEFO0 Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
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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 [5]
Amidox DM3D0WA N. A. N. A. Terminated [7]
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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 [6]
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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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 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.
6 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.
7 Metabolism of the new ribonucleotide reductase inhibitor amidox in the isolated perfused rat liver. Anticancer Res. 2000 Sep- Oct;20(5B):3521-6.