Target Information

Target General Infomation
Target ID
T37847
Former ID
TTDS00310
Target Name
DNA polymerase
Gene Name
UL30
Synonyms
DNA polymerase; Herpes simplex virus-specified DNA polymerase; UL30
Target Type
Successful
Disease Adult varicella zoster virus infection [ICD10: B02]
Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10: C91.0]
Cytomegalovirus infection [ICD10: B25]
Cytomegalovirus retinitis [ICD9: 78.5; ICD10: B25.8, H30.9]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Herpes simplex virus infection [ICD9: 54; ICD10: B00]
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]
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.
BioChemical Class
DNA polymerase type-B family
Target Validation
T37847
UniProt ID
P04293
EC Number
EC 2.7.7.7
Sequence
MFSGGGGPLSPGGKSAARAASGFFAPAGPRGASRGPPPCLRQNFYNPYLAPVGTQQKPTG
PTQRHTYYSECDEFRFIAPRVLDEDAPPEKRAGVHDGHLKRAPKVYCGGDERDVLRVGSG
GFWPRRSRLWGGVDHAPAGFNPTVTVFHVYDILENVEHAYGMRAAQFHARFMDAITPTGT
VITLLGLTPEGHRVAVHVYGTRQYFYMNKEEVDRHLQCRAPRDLCERMAAALRESPGASF
RGISADHFEAEVVERTDVYYYETRPALFYRVYVRSGRVLSYLCDNFCPAIKKYEGGVDAT
TRFILDNPGFVTFGWYRLKPGRNNTLAQPAAPMAFGTSSDVEFNCTADNLAIEGGMSDLP
AYKLMCFDIECKAGGEDELAFPVAGHPEDLVIQISCLLYDLSTTALEHVLLFSLGSCDLP
ESHLNELAARGLPTPVVLEFDSEFEMLLAFMTLVKQYGPEFVTGYNIINFDWPFLLAKLT
DIYKVPLDGYGRMNGRGVFRVWDIGQSHFQKRSKIKVNGMVNIDMYGIITDKIKLSSYKL
NAVAEAVLKDKKKDLSYRDIPAYYAAGPAQRGVIGEYCIQDSLLVGQLFFKFLPHLELSA
VARLAGINITRTIYDGQQIRVFTCLLRLADQKGFILPDTQGRFRGAGGEAPKRPAAARED
EERPEEEGEDEDEREEGGGEREPEGARETAGRHVGYQGARVLDPTSGFHVNPVVVFDFAS
LYPSIIQAHNLCFSTLSLRADAVAHLEAGKDYLEIEVGGRRLFFVKAHVRESLLSILLRD
WLAMRKQIRSRIPQSSPEEAVLLDKQQAAIKVVCNSVYGFTGVQHGLLPCLHVAATVTTI
GREMLLATREYVHARWAAFEQLLADFPEAADMRAPGPYSMRIIYGDTDSIFVLCRGLTAA
GLTAVGDKMASHISRALFLPPIKLECEKTFTKLLLIAKKKYIGVIYGGKMLIKGVDLVRK
NNCAFINRTSRALVDLLFYDDTVSGAAAALAERPAEEWLARPLPEGLQAFGAVLVDAHRR
ITDPERDIQDFVLTAELSRHPRAYTNKRLAHLTVYYKLMARRAQVPSIKDRIPYVIVAQT
REVEETVARLAALRELDAAAPGDEPAPPAALPSPAKRPRETPSPADPPGGASKPRKLLVS
ELAEDPAYAIAHGVALNTDYYFSHLLGAACVTFKALFGNNAKITESLLKRFIPEVWHPPD
DVAARLRTAGFGAVGAGATAEETRRMLHRAFDTLA
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 521412ClinicalTrials.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 521437ClinicalTrials.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 522061ClinicalTrials.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 522561ClinicalTrials.gov (NCT00831103) A Phase 2b Trial of EPB-348 for the Treatment of Herpes Zoster. U.S. National Institutes of Health.
Ref 523731ClinicalTrials.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 530906Incorporation of gemcitabine and cytarabine into DNA by DNA polymerase beta and ligase III/XRCC1. Biochemistry. 2010 Jun 15;49(23):4833-40.
Ref 536361Natural 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 536833Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
Ref 538237FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 071471.
Ref 538537FDA 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 544780Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001039)
Ref 544783Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001059)
Ref 545471Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003388)
Ref 545808Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004825)
Ref 547065Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012718)
Ref 549588Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800042373)
Ref 550782Drug information of Aciclovir, 2008. eduDrugs.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 525457Current pharmacological approaches to the therapy of varicella zoster virus infections: a guide to treatment. Drugs. 1999 Feb;57(2):187-206.
Ref 525549J Nat Prod. 1999 Jul;62(7):1000-2.Harbinatic acid, a novel and potent DNA polymerase beta inhibitor from Hardwickia binata.
Ref 525581J Nat Prod. 1999 Aug;62(8):1110-3.DNA polymerase beta inhibitors from Sandoricum koetjape.
Ref 525584Approaches and strategies for the treatment of influenza virus infections. Antivir Chem Chemother. 1999 Jul;10(4):155-85.
Ref 525684J Nat Prod. 1999 Dec;62(12):1624-6.DNA polymerase beta inhibitors from Baeckea gunniana.
Ref 525685J Nat Prod. 1999 Dec;62(12):1660-3.DNA polymerase beta inhibitors from Tetracera boiviniana.
Ref 525904J 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 526418Focus on new drugs in development against human cytomegalovirus. Drugs. 2002;62(13):1853-8.
Ref 527652J Nat Prod. 2005 Jul;68(7):979-84.Acylphloroglucinol derivatives from Mahurea palustris.
Ref 527897J Nat Prod. 2005 Nov;68(11):1625-8.(+)-Myristinins A and D from Knema elegans, which inhibit DNA polymerase beta and cleave DNA.
Ref 529247Bioorg 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 529449GS-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 529712J 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 529967Bioorg 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 533031Herpes simplex virus type 1 DNA polymerase. Mechanism of inhibition by acyclovir triphosphate. J Biol Chem. 1989 May 5;264(13):7405-11.
Ref 533563J Med Chem. 1980 Jan;23(1):34-8.Inhibitors of Bacillus subtilis DNA polymerase III. 6-Anilinouracils and 6-(alkylamino)uracils.
Ref 534117Fialuridine 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 536706Herpes 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 537088Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66. doi: 10.2165/00003495-200969020-00002.
Ref 537100Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient. Oral Microbiol Immunol. 2009 Apr;24(2):109-15.
Ref 537140Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22.
Ref 537233Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72.
Ref 537548Application 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 537737Inhibition 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 537796Selective binding of actinomycin D and distamycin A to DNA. Nucleic Acids Res. 1982 Nov 25;10(22):7273-82.
Ref 544014Conversion 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 544206Progress in the Development of New Therapies for Herpesvirus Infections. Curr Opin Virol. 2011 December 1; 1(6): 548-554.
Ref 550372Idenix Pharmaceuticals Advances HCV Discovery Program to Clinic. News for Idenix. 2008.
Ref 550886US patent application no. 2004,0023,290, Novel therapeutic agents that modulate enzymatic processes.
Ref 551352Differential 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 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551448Therapy with amineptine, a dopamine reuptake inhibitor, in patients with major depression. Indian J Psychiatry. 1997 Apr;39(2):147-53.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.