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 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]
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]
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
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
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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).
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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)
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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.
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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.
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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.
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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.
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Ref 537796Selective binding of actinomycin D and distamycin A to DNA. Nucleic Acids Res. 1982 Nov 25;10(22):7273-82.
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