Target Information
Target General Infomation | |||||
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Target ID |
T62553
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Former ID |
TTDS00246
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Target Name |
Ribonucleoside-diphosphate reductase
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Gene Name |
RIR1
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Synonyms |
Ribonucleoside diphosphate reductase; Ribonucleotide reductase; RIR1
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Target Type |
Successful
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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).
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BioChemical Class |
Oxidoreductases acting on CH or CH(2) groups
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Target Validation |
T62553
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UniProt ID | |||||
EC Number |
EC 1.17.4.1
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Sequence |
MASRPAASSPVEARAPVGGQEAGGPSAATQGEAAGAPLAHGHHVYCQRVNGVMVLSDKTP
GSASYRISDNNFVQCGSNCTMIIDGDVVRGRPQDPGAAASPAPFVAVTNIGAGSDGGTAV VAFGGTPRRSAGTSTGTQTADVPTEALGGPPPPPRFTLGGGCCSCRDTRRRSAVFGGEGD PVGPAEFVSDDRSSDSDSDDSEDTDSETLSHASSDVSGGATYDDALDSDSSSDDSLQIDG PVCRPWSNDTAPLDVCPGTPGPGADAGGPSAVDPHAPTPEAGAGLAADPAVARDDAEGLS DPRPRLGTGTAYPVPLELTPENAEAVARFLGDAVNREPALMLEYFCRCAREETKRVPPRT FGSPPRLTEDDFGLLNYALVEMQRLCLDVPPVPPNAYMPYYLREYVTRLVNGFKPLVSRS ARLYRILGVLVHLRIRTREASFEEWLRSKEVALDFGLTERLREHEAQLVILAQALDHYDC LIHSTPHTLVERGLQSALKYEEFYLKRFGGHYMESVFQMYTRIAGFLACRATRGMRHIAL GREGSWWEMFKFFFHRLYDHQIVPSTPAMLNLGTRNYYTSSCYLVNPQATTNKATLRAIT SNVSAILARNGGIGLCVQAFNDSGPGTASVMPALKVLDSLVAAHNKESARPTGACVYLEP WHTDVRAVLRMKGVLAGEEAQRCDNIFSALWMPDLFFKRLIRHLDGEKNVTWTLFDRDTS MSLADFHGEEFEKLYQHLEVMGFGEQIPIQELAYGIVRSAATTGSPFVMFKDAVNRHYIY DTQGAAIAGSNLCTEIVHPASKRSSGVCNLGSVNLARCVSRQTFDFGRLRDAVQACVLMV NIMIDSTLQPTPQCTRGNDNLRSMGIGMQGLHTACLKLGLDLESAEFQDLNKHIAEVMLL SAMKTSNALCVRGARPFNHFKRSMYRAGRFHWERFPDARPRYEGEWEMLRQSMMKHGLRN SQFVALMPTAASAQISDVSEGFAPLFTNLFSKVTRDGETLRPNTLLLKELERTFSGKRLL EVMDSLDAKQWSVAQALPCLEPTHPLRRFKTAFDYDQKLLIDLCADRAPYVDHSQSMTLY VTEKADGTLPASTLVRLLVHAYKRGLKTGMYYCKVRKATNSGVFGGDDNIVCMSCAL |
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Drugs and Mode of Action | |||||
Drug(s) | Clofarabine | Drug Info | Approved | Myelodysplastic syndrome; Acute lymphoblastic leukemia | [527466], [536361], [541885], [551871] |
G-207 virus construct | Drug Info | Phase 1/2 | Glioma | [521499] | |
Trimidox | Drug Info | Preclinical | Cancer | [545781] | |
Didox | Drug Info | Discontinued in Phase 2 | Cancer | [545210] | |
Amidox | Drug Info | Terminated | Discovery agent | [545422] | |
BILD-1263 | Drug Info | Terminated | Herpes simplex virus infection | [545734] | |
BILD-1351 | Drug Info | Terminated | Herpes simplex virus infection | [546192] | |
BILD-1357 | Drug Info | Terminated | Herpes simplex virus infection | [546590] | |
BILD-733 | Drug Info | Terminated | Herpes simplex virus infection | [545675] | |
References | |||||
Ref 521499 | 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 536361 | Natural 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 541885 | (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 545210 | 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 545422 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003197) | ||||
Ref 545675 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004139) | ||||
Ref 545734 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004429) | ||||
Ref 545781 | 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 546192 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006827) | ||||
Ref 527093 | Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal metastases. Ann Surg. 2004 Jun;239(6):892-9; discussion 899-902. | ||||
Ref 531689 | Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma. Chin J Cancer. 2011 Dec;30(12):831-41. | ||||
Ref 534081 | Resistance 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 534166 | Evaluation 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 534242 | Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity. J Med Chem. 1996 Oct 11;39(21):4173-80. | ||||
Ref 534712 | The 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 535094 | Metabolism of the new ribonucleotide reductase inhibitor amidox in the isolated perfused rat liver. Anticancer Res. 2000 Sep- Oct;20(5B):3521-6. | ||||
Ref 535574 | 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. |
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