Target Information
Target General Infomation | |||||
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Target ID |
T37847
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Former ID |
TTDS00310
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Target Name |
DNA polymerase
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Gene Name |
UL30
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Synonyms |
DNA polymerase; Herpes simplex virus-specified DNA polymerase; UL30
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Target Type |
Successful
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Disease | Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10: C91.0] | ||||
Adult varicella zoster virus infection [ICD10: B02] | |||||
Cytomegalovirus retinitis [ICD9: 78.5; ICD10: B25.8, H30.9] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Cytomegalovirus infection [ICD10: B25] | |||||
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2] | |||||
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26] | |||||
HBV infection [ICD9: 070.2-070.3; ICD10: B16, B18.0, B18.1] | |||||
Herpes simplex virus infection [ICD9: 54; ICD10: B00] | |||||
Melanoma [ICD9: 172; ICD10: C43] | |||||
Viral infections [ICD9: 054.0, 054.1, 054.2, 054.3, 075, 771.2, 052, 053; ICD10: B01, B02, A60, B00, B27, G05.1, P35.2] | |||||
Function |
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA- binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication.
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BioChemical Class |
DNA polymerase type-B family
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Target Validation |
T37847
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UniProt ID | |||||
EC Number |
EC 2.7.7.7
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Sequence |
MFSGGGGPLSPGGKSAARAASGFFAPAGPRGASRGPPPCLRQNFYNPYLAPVGTQQKPTG
PTQRHTYYSECDEFRFIAPRVLDEDAPPEKRAGVHDGHLKRAPKVYCGGDERDVLRVGSG GFWPRRSRLWGGVDHAPAGFNPTVTVFHVYDILENVEHAYGMRAAQFHARFMDAITPTGT VITLLGLTPEGHRVAVHVYGTRQYFYMNKEEVDRHLQCRAPRDLCERMAAALRESPGASF RGISADHFEAEVVERTDVYYYETRPALFYRVYVRSGRVLSYLCDNFCPAIKKYEGGVDAT TRFILDNPGFVTFGWYRLKPGRNNTLAQPAAPMAFGTSSDVEFNCTADNLAIEGGMSDLP AYKLMCFDIECKAGGEDELAFPVAGHPEDLVIQISCLLYDLSTTALEHVLLFSLGSCDLP ESHLNELAARGLPTPVVLEFDSEFEMLLAFMTLVKQYGPEFVTGYNIINFDWPFLLAKLT DIYKVPLDGYGRMNGRGVFRVWDIGQSHFQKRSKIKVNGMVNIDMYGIITDKIKLSSYKL NAVAEAVLKDKKKDLSYRDIPAYYAAGPAQRGVIGEYCIQDSLLVGQLFFKFLPHLELSA VARLAGINITRTIYDGQQIRVFTCLLRLADQKGFILPDTQGRFRGAGGEAPKRPAAARED EERPEEEGEDEDEREEGGGEREPEGARETAGRHVGYQGARVLDPTSGFHVNPVVVFDFAS LYPSIIQAHNLCFSTLSLRADAVAHLEAGKDYLEIEVGGRRLFFVKAHVRESLLSILLRD WLAMRKQIRSRIPQSSPEEAVLLDKQQAAIKVVCNSVYGFTGVQHGLLPCLHVAATVTTI GREMLLATREYVHARWAAFEQLLADFPEAADMRAPGPYSMRIIYGDTDSIFVLCRGLTAA GLTAVGDKMASHISRALFLPPIKLECEKTFTKLLLIAKKKYIGVIYGGKMLIKGVDLVRK NNCAFINRTSRALVDLLFYDDTVSGAAAALAERPAEEWLARPLPEGLQAFGAVLVDAHRR ITDPERDIQDFVLTAELSRHPRAYTNKRLAHLTVYYKLMARRAQVPSIKDRIPYVIVAQT REVEETVARLAALRELDAAAPGDEPAPPAALPSPAKRPRETPSPADPPGGASKPRKLLVS ELAEDPAYAIAHGVALNTDYYFSHLLGAACVTFKALFGNNAKITESLLKRFIPEVWHPPD DVAARLRTAGFGAVGAGATAEETRRMLHRAFDTLA |
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Drugs and Mode of Action | |||||
Drug(s) | Aciclovir | Drug Info | Approved | Viral infections | [468061], [550782] |
Cidofovir | Drug Info | Approved | Cytomegalovirus infection | [536833] | |
Cytarabine | Drug Info | Approved | Acute lymphoblastic leukemia | [468059], [530906], [538237] | |
Foscavir | Drug Info | Approved | Cytomegalovirus retinitis | [538537] | |
Ganciclovir | Drug Info | Approved | Viral infections | [536361] | |
Penciclovir | Drug Info | Approved | Human immunodeficiency virus infection | [536361], [551871] | |
Valaciclovir | Drug Info | Approved | Viral infections | [468056], [536361] | |
Valacyclovir Hydrochloride | Drug Info | Approved | Herpes simplex virus infection | [551871] | |
Valganciclovir | Drug Info | Approved | Viral infections | [467957], [536361] | |
Netivudine | Drug Info | Phase 3 | Viral infections | [521437] | |
Fialuridine | Drug Info | Phase 2 | HBV infection | [521412] | |
Valomaciclovir stearate | Drug Info | Phase 2 | Adult varicella zoster virus infection | [522561] | |
GS-9219 | Drug Info | Phase 1/2 | Cancer | [522061] | |
BETULINIC ACID | Drug Info | Phase 1 | Melanoma | [540567] | |
Guanosine | Drug Info | Phase 1 | Discovery agent | [467804], [523731] | |
ROCICLOVIR | Drug Info | Phase 1 | Viral infections | [544783] | |
IDX136 | Drug Info | Preclinical | HCV infection | [549588] | |
Tomeglovir | Drug Info | Discontinued in Phase 2 | Viral infections | [547065] | |
CHPMPC | Drug Info | Discontinued in Phase 1 | Viral infections | [545808] | |
Amitivir | Drug Info | Terminated | Viral infections | [544780] | |
GR-95168 | Drug Info | Terminated | Viral infections | [545471] | |
Inhibitor | (+)-Myristinin A | Drug Info | [527897] | ||
(+)-Myristinin D | Drug Info | [527897] | |||
(24E)-3beta-hydroxy-7,24-euphadien-26-oic acid | Drug Info | [525904] | |||
2'-deoxythymidine triphosphate | Drug Info | [537737] | |||
3-cis-p-coumaroyl maslinic acid | Drug Info | [525685] | |||
3-Oximo-olean-12-en-29-oic acid | Drug Info | [525581] | |||
3-trans-p-coumaroyl maslinic acid | Drug Info | [525685] | |||
3alpha-O-trans-p-coumaroyl-7-labden-15-oic acid | Drug Info | [525549] | |||
3beta-hydroxyrus-12,19(29)-dien-28-oic acid | Drug Info | [525684] | |||
3beta-hydroxyrus-18,20(30)-dien-28-oic acid | Drug Info | [525684] | |||
5-propenyl-2'-deoxyuridine triphosphate | Drug Info | [537737] | |||
5-propenyl-arabinofuranosyluracil 5'-triphosphate | Drug Info | [537737] | |||
6-(3-Ethyl-phenylamino)-1H-pyrimidine-2,4-dione | Drug Info | [533563] | |||
6-(4-Bromo-phenylamino)-1H-pyrimidine-2,4-dione | Drug Info | [533563] | |||
6-(4-Chloro-phenylamino)-1H-pyrimidine-2,4-dione | Drug Info | [533563] | |||
Actinomycin D | Drug Info | [537796] | |||
Alpha,beta-methylene-dATP | Drug Info | [529712] | |||
Alpha,beta-methylene-dCTP | Drug Info | [529712] | |||
Alpha,beta-methylene-dGTP | Drug Info | [529712] | |||
Alpha,beta-methylene-dTTP | Drug Info | [529712] | |||
BETULINIC ACID | Drug Info | [525685] | |||
Cytarabine | Drug Info | [537233] | |||
DdCTP SODIUM | Drug Info | [527652] | |||
Foscavir | Drug Info | [537140] | |||
Gallic acid 5,6-dihydroxy-3-carboxyphenylester | Drug Info | [551352] | |||
Ganciclovir | Drug Info | [537548] | |||
GS-9219 | Drug Info | [529449] | |||
Guanosine | Drug Info | [551393] | |||
Guanosine-5'-Monophosphate | Drug Info | [551393] | |||
IDX136 | Drug Info | [550372], [551448] | |||
Mahureone D | Drug Info | [527652] | |||
OLEANOLIC_ACID | Drug Info | [525684] | |||
Penciclovir | Drug Info | [537088] | |||
PENICILLIOL A | Drug Info | [529967] | |||
PMEA | Drug Info | [536706] | |||
TALAROFLAVONE | Drug Info | [529247] | |||
Tomeglovir | Drug Info | [526418] | |||
URSOLIC ACID | Drug Info | [525684] | |||
Valaciclovir | Drug Info | [537100] | |||
Valganciclovir | Drug Info | [537140] | |||
Modulator | Aciclovir | Drug Info | [556264] | ||
Amitivir | Drug Info | [525584] | |||
CHPMPC | Drug Info | [544014] | |||
Cidofovir | Drug Info | [556264] | |||
Fialuridine | Drug Info | [534117] | |||
GR-95168 | Drug Info | [550886] | |||
Netivudine | Drug Info | [525457] | |||
ROCICLOVIR | Drug Info | [533031], [551871] | |||
Valacyclovir Hydrochloride | Drug Info | [556264] | |||
Valomaciclovir stearate | Drug Info | [544206] | |||
References | |||||
Ref 467804 | (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: 4567). | ||||
Ref 467957 | (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: 4716). | ||||
Ref 468056 | (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: 4824). | ||||
Ref 468059 | (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: 4827). | ||||
Ref 468061 | (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: 4829). | ||||
Ref 521412 | ClinicalTrials.gov (NCT00000654) The Tolerance of HIV-Infected Patients With Herpes Group Virus Infections to Oral Doses of FIAU. U.S. National Institutes of Health. | ||||
Ref 521437 | ClinicalTrials.gov (NCT00002315) A Comparison of 882C87 Versus Acyclovir in the Treatment of Herpes Zoster in Patients With Weakened Immune Systems. U.S. National Institutes of Health. | ||||
Ref 522061 | ClinicalTrials.gov (NCT00499239) A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM). U.S. National Institutes of Health. | ||||
Ref 522561 | ClinicalTrials.gov (NCT00831103) A Phase 2b Trial of EPB-348 for the Treatment of Herpes Zoster. U.S. National Institutes of Health. | ||||
Ref 523731 | ClinicalTrials.gov (NCT01493570) Assessment of Exposure of BI 409306 in Cerebrospinal Fluid (CSF) Relative to Plasma as Well as to Evaluation of the Effect of Different Doses of BI 409306 on the cGMP(Cyclic Guanosine Monophosphate) Levels in CSF in Healthy Male Volunteers. U.S. National Institutes of Health. | ||||
Ref 530906 | Incorporation of gemcitabine and cytarabine into DNA by DNA polymerase beta and ligase III/XRCC1. Biochemistry. 2010 Jun 15;49(23):4833-40. | ||||
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 538237 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 071471. | ||||
Ref 538537 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020068. | ||||
Ref 540567 | (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: 3945). | ||||
Ref 544780 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001039) | ||||
Ref 544783 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001059) | ||||
Ref 545471 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003388) | ||||
Ref 545808 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004825) | ||||
Ref 547065 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012718) | ||||
Ref 525457 | Current pharmacological approaches to the therapy of varicella zoster virus infections: a guide to treatment. Drugs. 1999 Feb;57(2):187-206. | ||||
Ref 525549 | J Nat Prod. 1999 Jul;62(7):1000-2.Harbinatic acid, a novel and potent DNA polymerase beta inhibitor from Hardwickia binata. | ||||
Ref 525581 | J Nat Prod. 1999 Aug;62(8):1110-3.DNA polymerase beta inhibitors from Sandoricum koetjape. | ||||
Ref 525584 | Approaches and strategies for the treatment of influenza virus infections. Antivir Chem Chemother. 1999 Jul;10(4):155-85. | ||||
Ref 525685 | J Nat Prod. 1999 Dec;62(12):1660-3.DNA polymerase beta inhibitors from Tetracera boiviniana. | ||||
Ref 525904 | J Nat Prod. 2000 Oct;63(10):1356-60.A new 7,8-euphadien-type triterpenoid from Brackenridgea nitida and Bleasdalea bleasdalei that inhibits DNA polymerase beta. | ||||
Ref 526418 | Focus on new drugs in development against human cytomegalovirus. Drugs. 2002;62(13):1853-8. | ||||
Ref 527897 | J Nat Prod. 2005 Nov;68(11):1625-8.(+)-Myristinins A and D from Knema elegans, which inhibit DNA polymerase beta and cleave DNA. | ||||
Ref 529247 | Bioorg Med Chem. 2008 Mar 15;16(6):2939-44. Epub 2007 Dec 25.1-deoxyrubralactone, a novel specific inhibitor of families X and Y of eukaryotic DNA polymerases from a fungal strain derived from sea algae. | ||||
Ref 529449 | GS-9219--a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin's lymphoma. Clin Cancer Res. 2008 May 1;14(9):2824-32. | ||||
Ref 529712 | J Med Chem. 2008 Oct 23;51(20):6460-70. Epub 2008 Sep 24.Alpha,beta-methylene-2'-deoxynucleoside 5'-triphosphates as noncleavable substrates for DNA polymerases: isolation, characterization, and stability studies of novel 2'-deoxycyclonucleosides, 3,5'-cyclo-dG, and 2,5'-cyclo-dT. | ||||
Ref 529967 | Bioorg Med Chem. 2009 Mar 1;17(5):1811-6. Epub 2009 Feb 1.Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. | ||||
Ref 533031 | Herpes simplex virus type 1 DNA polymerase. Mechanism of inhibition by acyclovir triphosphate. J Biol Chem. 1989 May 5;264(13):7405-11. | ||||
Ref 533563 | J Med Chem. 1980 Jan;23(1):34-8.Inhibitors of Bacillus subtilis DNA polymerase III. 6-Anilinouracils and 6-(alkylamino)uracils. | ||||
Ref 534117 | Fialuridine and its metabolites inhibit DNA polymerase gamma at sites of multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial structural defects in cultured hepatoblasts. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3592-7. | ||||
Ref 536706 | Herpes simplex virus-specified DNA polymerase is the target for the antiviral action of 9-(2-phosphonylmethoxyethyl)adenine. J Biol Chem. 1991 Jan 5;266(1):238-44. | ||||
Ref 537088 | Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66. doi: 10.2165/00003495-200969020-00002. | ||||
Ref 537100 | Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient. Oral Microbiol Immunol. 2009 Apr;24(2):109-15. | ||||
Ref 537140 | Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22. | ||||
Ref 537233 | Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72. | ||||
Ref 537548 | Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009 Feb;30(2):77-81. | ||||
Ref 537737 | Inhibition of human hepatitis B virus DNA polymerase and duck hepatitis B virus DNA polymerase by triphosphates of thymidine analogs and pharmacokinetic properties of the corresponding nucleosides. JMed Virol. 1988 Dec;26(4):353-62. | ||||
Ref 537796 | Selective binding of actinomycin D and distamycin A to DNA. Nucleic Acids Res. 1982 Nov 25;10(22):7273-82. | ||||
Ref 544014 | Conversion of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine to cidofovir by an intracellular cyclic CMP phosphodiesterase.. Antimicrob Agents Chemother. 1997 March; 41(3): 641-646. | ||||
Ref 544206 | Progress in the Development of New Therapies for Herpesvirus Infections. Curr Opin Virol. 2011 December 1; 1(6): 548-554. | ||||
Ref 550886 | US patent application no. 2004,0023,290, Novel therapeutic agents that modulate enzymatic processes. | ||||
Ref 551352 | Differential inhibition of reverse transcriptase and various DNA polymerases by digallic acid and its derivatives. J Nat Prod. 1990 Sep-Oct;53(5):1234-40. | ||||
Ref 551448 | Therapy with amineptine, a dopamine reuptake inhibitor, in patients with major depression. Indian J Psychiatry. 1997 Apr;39(2):147-53. |
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