Target Information
| Target General Information | Top | |||||
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| Target ID |
T73342
(Former ID: TTDS00246)
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| Target Name |
Ribonucleotide reductase (RIR)
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| Synonyms |
Ribonucleoside diphosphate reductase; RIR1
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| Gene Name |
RIR
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Mature B-cell lymphoma [ICD-11: 2A85] | |||||
| 2 | Myelodysplastic syndrome [ICD-11: 2A37] | |||||
| 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.
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| BioChemical Class |
CH/CH(2) oxidoreductase
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| UniProt ID | ||||||
| Sequence |
MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLA
AETAATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMEDLYNYINPHNGKHSPMVAKST LDIVLANKDRLNSAIIYDRDFSYNYFGFKTLERSYLLKINGKVAERPQHMLMRVSVGIHK EDIDAAIETYNLLSERWFTHASPTLFNAGTNRPQLSSCFLLSMKDDSIEGIYDTLKQCAL ISKSAGGIGVAVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNKRPGAFAIY LEPWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMCPNECPGLD EVWGEEFEKLYASYEKQGRVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNL GTIKCSNLCTEIVEYTSKDEVAVCNLASLALNMYVTSEHTYDFKKLAEVTKVVVRNLNKI IDINYYPVPEACLSNKRHRPIGIGVQGLADAFILMRYPFESAEAQLLNKQIFETIYYGAL EASCDLAKEQGPYETYEGSPVSKGILQYDMWNVTPTDLWDWKVLKEKIAKYGIRNSLLIA PMPTASTAQILGNNESIEPYTSNIYTRRVLSGEFQIVNPHLLKDLTERGLWHEEMKNQII ACNGSIQSIPEIPDDLKQLYKTVWEISQKTVLKMAAERGAFIDQSQSLNIHIAEPNYGKL TSMHFYGWKQGLKTGMYYLRTRPAANPIQFTLNKEKLKDKEKVSKEEEEKERNTAAMVCS LENRDECLMCGS Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Clofarabine | Drug Info | Approved | Acute lymphoblastic leukaemia | [2], [3], [4], [5] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | CPX-POM | Drug Info | Phase 2 | Bladder cancer | [6] | |
| 2 | G-207 virus construct | Drug Info | Phase 1/2 | Glioma | [7] | |
| 3 | COH29 | Drug Info | Phase 1 | Solid tumour/cancer | [8] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Didox | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [9] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | Trimidox | Drug Info | Preclinical | Solid tumour/cancer | [10] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 7 Inhibitor drugs | + | ||||
| 1 | Clofarabine | Drug Info | [1] | |||
| 2 | CPX-POM | Drug Info | [11] | |||
| 3 | G-207 virus construct | Drug Info | [12], [13] | |||
| 4 | COH29 | Drug Info | [8] | |||
| 5 | Didox | Drug Info | [14] | |||
| 6 | Trimidox | Drug Info | [15] | |||
| 7 | Amidox | Drug Info | [16] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6802). | |||||
| REF 3 | 2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 6 | ClinicalTrials.gov (NCT04525131) Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT00028158) Safety and Effectiveness Study of G207, a Tumor-Killing Virus, in Patients With Recurrent Brain Cancer. U.S. National Institutes of Health. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002464) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004681) | |||||
| REF 11 | Preclinical Pharmacokinetics of Fosciclopirox, a Novel Treatment of Urothelial Cancers, in Rats and Dogs. J Pharmacol Exp Ther. 2019 Aug;370(2):148-159. | |||||
| REF 12 | Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma. Chin J Cancer. 2011 Dec;30(12):831-41. | |||||
| REF 13 | Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal metastases. Ann Surg. 2004 Jun;239(6):892-9; discussion 899-902. | |||||
| REF 14 | 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. | |||||
| REF 15 | 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. | |||||
| REF 16 | Metabolism of the new ribonucleotide reductase inhibitor amidox in the isolated perfused rat liver. Anticancer Res. 2000 Sep- Oct;20(5B):3521-6. | |||||
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