Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIU7X1)

DTT Name Herpes simplex virus DNA polymerase UL30 (HSV UL30)
Synonyms HSV DNA polymerase catalytic subunit
Gene Name HSV UL30
DTT Type
Successful target
 [1]
BioChemical Class
DNA polymerase type-B
UniProt ID
DPOL_HHV11
TTD ID
T37847
Sequence
MFSGGGGPLSPGGKSAARAASGFFAPAGPRGASRGPPPCLRQNFYNPYLAPVGTQQKPTG
PTQRHTYYSECDEFRFIAPRVLDEDAPPEKRAGVHDGHLKRAPKVYCGGDERDVLRVGSG
GFWPRRSRLWGGVDHAPAGFNPTVTVFHVYDILENVEHAYGMRAAQFHARFMDAITPTGT
VITLLGLTPEGHRVAVHVYGTRQYFYMNKEEVDRHLQCRAPRDLCERMAAALRESPGASF
RGISADHFEAEVVERTDVYYYETRPALFYRVYVRSGRVLSYLCDNFCPAIKKYEGGVDAT
TRFILDNPGFVTFGWYRLKPGRNNTLAQPAAPMAFGTSSDVEFNCTADNLAIEGGMSDLP
AYKLMCFDIECKAGGEDELAFPVAGHPEDLVIQISCLLYDLSTTALEHVLLFSLGSCDLP
ESHLNELAARGLPTPVVLEFDSEFEMLLAFMTLVKQYGPEFVTGYNIINFDWPFLLAKLT
DIYKVPLDGYGRMNGRGVFRVWDIGQSHFQKRSKIKVNGMVNIDMYGIITDKIKLSSYKL
NAVAEAVLKDKKKDLSYRDIPAYYAAGPAQRGVIGEYCIQDSLLVGQLFFKFLPHLELSA
VARLAGINITRTIYDGQQIRVFTCLLRLADQKGFILPDTQGRFRGAGGEAPKRPAAARED
EERPEEEGEDEDEREEGGGEREPEGARETAGRHVGYQGARVLDPTSGFHVNPVVVFDFAS
LYPSIIQAHNLCFSTLSLRADAVAHLEAGKDYLEIEVGGRRLFFVKAHVRESLLSILLRD
WLAMRKQIRSRIPQSSPEEAVLLDKQQAAIKVVCNSVYGFTGVQHGLLPCLHVAATVTTI
GREMLLATREYVHARWAAFEQLLADFPEAADMRAPGPYSMRIIYGDTDSIFVLCRGLTAA
GLTAVGDKMASHISRALFLPPIKLECEKTFTKLLLIAKKKYIGVIYGGKMLIKGVDLVRK
NNCAFINRTSRALVDLLFYDDTVSGAAAALAERPAEEWLARPLPEGLQAFGAVLVDAHRR
ITDPERDIQDFVLTAELSRHPRAYTNKRLAHLTVYYKLMARRAQVPSIKDRIPYVIVAQT
REVEETVARLAALRELDAAAPGDEPAPPAALPSPAKRPRETPSPADPPGGASKPRKLLVS
ELAEDPAYAIAHGVALNTDYYFSHLLGAACVTFKALFGNNAKITESLLKRFIPEVWHPPD
DVAARLRTAGFGAVGAGATAEETRRMLHRAFDTLA
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.

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
10 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aciclovir DMYLOVR Genital herpes 1A94 Approved [2]
Cidofovir DMA13GD Cytomegalovirus infection 1D82 Approved [2]
Cytarabine DMZD5QR Acute lymphoblastic leukaemia 2A85 Approved [3]
Famciclovir DMJHLSD Meniere disease AB31.0 Approved [4]
Foscavir DM9KJLZ Cytomegalovirus retinitis 9B72.00 Approved [5]
Ganciclovir DM1MBYQ Cytomegalovirus infection 1D82 Approved [6]
Penciclovir DMOUMDV Herpes simplex labialis 1F00.01 Approved [1]
Valaciclovir DMHKS94 Genital herpes 1A94 Approved [7]
Valacyclovir Hydrochloride DM5I1CE Herpes simplex virus infection 1F00 Approved [2]
Valganciclovir DMS2IUH Virus infection 1A24-1D9Z Approved [5]
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⏷ Show the Full List of 10 Approved Drug(s)
8 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Netivudine DMTKRY1 Virus infection 1A24-1D9Z Phase 3 [8]
Fialuridine DMCIGRB Hepatitis B virus infection 1E51.0 Phase 2 [9]
URSOLIC ACID DM4SOAW Metabolic syndrome x 5C50-5D2Z Phase 2 [10]
Valomaciclovir stearate DMAEB9O Varicella zoster virus infection 1E91 Phase 2 [11]
GS-9219 DMTJQ8S Solid tumour/cancer 2A00-2F9Z Phase 1/2 [12]
BETULINIC ACID DMBUI2A Melanoma 2C30 Phase 1 [13]
Guanosine DM4T5LH N. A. N. A. Phase 1 [14]
ROCICLOVIR DMDRBNJ Virus infection 1A24-1D9Z Phase 1 [15]
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⏷ Show the Full List of 8 Clinical Trial Drug(s)
5 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tomeglovir DMY40KZ Virus infection 1A24-1D9Z Discontinued in Phase 2 [16]
Aphidicolin DM71C6D N. A. N. A. Discontinued in Phase 1 [17]
CHPMPC DMJ5UYL Virus infection 1A24-1D9Z Discontinued in Phase 1 [18]
Amitivir DM64YJW Virus infection 1A24-1D9Z Terminated [20]
GR-95168 DMAHNF6 Virus infection 1A24-1D9Z Terminated [21]
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1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
IDX136 DMRIMZL Hepatitis C virus infection 1E51.1 Preclinical [19]
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27 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(+)-Myristinin A DM7FZHI Discovery agent N.A. Investigative [22]
(+)-Myristinin D DMEK07T Discovery agent N.A. Investigative [22]
(24E)-3beta-hydroxy-7,24-euphadien-26-oic acid DM1RYH9 Discovery agent N.A. Investigative [23]
2'-deoxythymidine triphosphate DM9OEJT Discovery agent N.A. Investigative [24]
3-cis-p-coumaroyl maslinic acid DM78FWG Discovery agent N.A. Investigative [13]
3-Oximo-olean-12-en-29-oic acid DMVIRLX Discovery agent N.A. Investigative [25]
3-trans-p-coumaroyl maslinic acid DMOQWDS Discovery agent N.A. Investigative [13]
3alpha-O-trans-p-coumaroyl-7-labden-15-oic acid DM4M6LR Discovery agent N.A. Investigative [26]
3beta-hydroxyrus-12,19(29)-dien-28-oic acid DML8NY0 Discovery agent N.A. Investigative [10]
3beta-hydroxyrus-18,20(30)-dien-28-oic acid DMKL59W Discovery agent N.A. Investigative [10]
5-propenyl-2'-deoxyuridine triphosphate DM6A902 Discovery agent N.A. Investigative [24]
5-propenyl-arabinofuranosyluracil 5'-triphosphate DM762FY Discovery agent N.A. Investigative [24]
6-(3-Ethyl-phenylamino)-1H-pyrimidine-2,4-dione DMKUHN9 Discovery agent N.A. Investigative [27]
6-(4-Bromo-phenylamino)-1H-pyrimidine-2,4-dione DMCYQDU Discovery agent N.A. Investigative [27]
6-(4-Chloro-phenylamino)-1H-pyrimidine-2,4-dione DM5LUF4 Discovery agent N.A. Investigative [27]
Alpha,beta-methylene-dATP DMHRME4 Discovery agent N.A. Investigative [28]
Alpha,beta-methylene-dCTP DMJI8TX Discovery agent N.A. Investigative [28]
Alpha,beta-methylene-dGTP DMPZS80 Discovery agent N.A. Investigative [28]
Alpha,beta-methylene-dTTP DMPAHJF Discovery agent N.A. Investigative [28]
DdCTP SODIUM DMHLNA2 Discovery agent N.A. Investigative [29]
Gallic acid 5,6-dihydroxy-3-carboxyphenylester DMNWU83 Discovery agent N.A. Investigative [30]
Guanosine-5'-Monophosphate DM3SLZK Discovery agent N.A. Investigative [14]
Mahureone D DM5WNH8 Discovery agent N.A. Investigative [29]
OLEANOLIC_ACID DMWDMJ3 Discovery agent N.A. Investigative [10]
PENICILLIOL A DMZUES2 Discovery agent N.A. Investigative [31]
PMEA DMBKVJY Discovery agent N.A. Investigative [32]
TALAROFLAVONE DMW24JP Discovery agent N.A. Investigative [33]
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⏷ Show the Full List of 27 Investigative Drug(s)

References

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9 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.
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21 US patent application no. 2004,0023,290, Novel therapeutic agents that modulate enzymatic processes.
22 (+)-Myristinins A and D from Knema elegans, which inhibit DNA polymerase beta and cleave DNA. J Nat Prod. 2005 Nov;68(11):1625-8.
23 A new 7,8-euphadien-type triterpenoid from Brackenridgea nitida and Bleasdalea bleasdalei that inhibits DNA polymerase beta. J Nat Prod. 2000 Oct;63(10):1356-60.
24 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.
25 DNA polymerase beta inhibitors from Sandoricum koetjape. J Nat Prod. 1999 Aug;62(8):1110-3.
26 Harbinatic acid, a novel and potent DNA polymerase beta inhibitor from Hardwickia binata. J Nat Prod. 1999 Jul;62(7):1000-2.
27 Inhibitors of Bacillus subtilis DNA polymerase III. 6-Anilinouracils and 6-(alkylamino)uracils. J Med Chem. 1980 Jan;23(1):34-8.
28 Alpha,beta-methylene-2'-deoxynucleoside 5'-triphosphates as noncleavable substrates for DNA polymerases: isolation, characterization, and stability... J Med Chem. 2008 Oct 23;51(20):6460-70.
29 Acylphloroglucinol derivatives from Mahurea palustris. J Nat Prod. 2005 Jul;68(7):979-84.
30 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.
31 Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. Bioorg Med Chem. 2009 Mar 1;17(5):1811-6.
32 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.
33 1-deoxyrubralactone, a novel specific inhibitor of families X and Y of eukaryotic DNA polymerases from a fungal strain derived from sea algae. Bioorg Med Chem. 2008 Mar 15;16(6):2939-44.