Target Information

Target General Infomation
Target ID
T62553
Former ID
TTDS00246
Target Name
Ribonucleoside-diphosphate reductase
Gene Name
RIR1
Synonyms
Ribonucleoside diphosphate reductase; Ribonucleotide reductase; RIR1
Target Type
Successful
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Glioma [ICD9: 191; ICD10: C71]
Herpes simplex virus infection [ICD9: 54; ICD10: B00]
Myelodysplastic syndrome; Acute lymphoblastic leukemia [ICD9:238.7, 204.0, 556; ICD10: D46, C91.0]
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 (By similarity).
BioChemical Class
Oxidoreductases acting on CH or CH(2) groups
Target Validation
T62553
UniProt ID
P08543
EC Number
EC 1.17.4.1
Sequence
MASRPAASSPVEARAPVGGQEAGGPSAATQGEAAGAPLAHGHHVYCQRVNGVMVLSDKTP
GSASYRISDNNFVQCGSNCTMIIDGDVVRGRPQDPGAAASPAPFVAVTNIGAGSDGGTAV
VAFGGTPRRSAGTSTGTQTADVPTEALGGPPPPPRFTLGGGCCSCRDTRRRSAVFGGEGD
PVGPAEFVSDDRSSDSDSDDSEDTDSETLSHASSDVSGGATYDDALDSDSSSDDSLQIDG
PVCRPWSNDTAPLDVCPGTPGPGADAGGPSAVDPHAPTPEAGAGLAADPAVARDDAEGLS
DPRPRLGTGTAYPVPLELTPENAEAVARFLGDAVNREPALMLEYFCRCAREETKRVPPRT
FGSPPRLTEDDFGLLNYALVEMQRLCLDVPPVPPNAYMPYYLREYVTRLVNGFKPLVSRS
ARLYRILGVLVHLRIRTREASFEEWLRSKEVALDFGLTERLREHEAQLVILAQALDHYDC
LIHSTPHTLVERGLQSALKYEEFYLKRFGGHYMESVFQMYTRIAGFLACRATRGMRHIAL
GREGSWWEMFKFFFHRLYDHQIVPSTPAMLNLGTRNYYTSSCYLVNPQATTNKATLRAIT
SNVSAILARNGGIGLCVQAFNDSGPGTASVMPALKVLDSLVAAHNKESARPTGACVYLEP
WHTDVRAVLRMKGVLAGEEAQRCDNIFSALWMPDLFFKRLIRHLDGEKNVTWTLFDRDTS
MSLADFHGEEFEKLYQHLEVMGFGEQIPIQELAYGIVRSAATTGSPFVMFKDAVNRHYIY
DTQGAAIAGSNLCTEIVHPASKRSSGVCNLGSVNLARCVSRQTFDFGRLRDAVQACVLMV
NIMIDSTLQPTPQCTRGNDNLRSMGIGMQGLHTACLKLGLDLESAEFQDLNKHIAEVMLL
SAMKTSNALCVRGARPFNHFKRSMYRAGRFHWERFPDARPRYEGEWEMLRQSMMKHGLRN
SQFVALMPTAASAQISDVSEGFAPLFTNLFSKVTRDGETLRPNTLLLKELERTFSGKRLL
EVMDSLDAKQWSVAQALPCLEPTHPLRRFKTAFDYDQKLLIDLCADRAPYVDHSQSMTLY
VTEKADGTLPASTLVRLLVHAYKRGLKTGMYYCKVRKATNSGVFGGDDNIVCMSCAL
Drugs and Mode of Action
Drug(s) Clofarabine Drug Info Approved Myelodysplastic syndrome; Acute lymphoblastic leukemia [1], [2], [3], [4]
G-207 virus construct Drug Info Phase 1/2 Glioma [5]
Trimidox Drug Info Preclinical Cancer [6]
Didox Drug Info Discontinued in Phase 2 Cancer [7]
Amidox Drug Info Terminated Discovery agent [8]
BILD-1263 Drug Info Terminated Herpes simplex virus infection [9]
BILD-1351 Drug Info Terminated Herpes simplex virus infection [10]
BILD-1357 Drug Info Terminated Herpes simplex virus infection [11]
BILD-733 Drug Info Terminated Herpes simplex virus infection [12]
Inhibitor Amidox Drug Info [13]
BILD-1263 Drug Info [14]
BILD-1351 Drug Info [15]
BILD-1357 Drug Info [16]
BILD-733 Drug Info [17]
Clofarabine Drug Info [18]
Didox Drug Info [19]
G-207 virus construct Drug Info [20], [21]
Trimidox Drug Info [22]
References
REF 12004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.
REF 2Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 3(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 4Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 5ClinicalTrials.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 6Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004681)
REF 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002464)
REF 8Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003197)
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004429)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006827)
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009082)
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004139)
REF 13Metabolism of the new ribonucleotide reductase inhibitor amidox in the isolated perfused rat liver. Anticancer Res. 2000 Sep- Oct;20(5B):3521-6.
REF 14Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease. Antimicrob Agents Chemother. 1996 May;40(5):1078-84.
REF 15The antiviral activity of the ribonucleotide reductase inhibitor BILD 1351 SE in combination with acyclovir against HSV type-1 in cell culture. Antiviral Res. 1998 Jul;39(1):35-46.
REF 16Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity. J Med Chem. 1996 Oct 11;39(21):4173-80.
REF 17Resistance of herpes simplex virus type 1 to peptidomimetic ribonucleotide reductase inhibitors: selection and characterization of mutant isolates. J Virol. 1996 Feb;70(2):787-93.
REF 18Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
REF 19Didox (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 20Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal metastases. Ann Surg. 2004 Jun;239(6):892-9; discussion 899-902.
REF 21Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma. Chin J Cancer. 2011 Dec;30(12):831-41.
REF 22Suppression 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.

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