Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMJX4U)

• DTT Name: Herpes simplex virus Ribonucleoside-diphosphate reductase (HSV RIR1)
• Synonyms: HSV Ribonucleotide reductase; HSV Ribonucleoside diphosphate reductase; HSV RIR1
• Gene Name: HSV RIR1
• DTT Type: Discontinued target; [1]
• BioChemical Class: CH/CH(2) oxidoreductase
• UniProt ID: RIR1_HHV11
• TTD ID: T62553
• Sequence:
  MASRPAASSPVEARAPVGGQEAGGPSAATQGEAAGAPLAHGHHVYCQRVNGVMVLSDKTP
  GSASYRISDNNFVQCGSNCTMIIDGDVVRGRPQDPGAAASPAPFVAVTNIGAGSDGGTAV
  VAFGGTPRRSAGTSTGTQTADVPTEALGGPPPPPRFTLGGGCCSCRDTRRRSAVFGGEGD
  PVGPAEFVSDDRSSDSDSDDSEDTDSETLSHASSDVSGGATYDDALDSDSSSDDSLQIDG
  PVCRPWSNDTAPLDVCPGTPGPGADAGGPSAVDPHAPTPEAGAGLAADPAVARDDAEGLS
  DPRPRLGTGTAYPVPLELTPENAEAVARFLGDAVNREPALMLEYFCRCAREETKRVPPRT
  FGSPPRLTEDDFGLLNYALVEMQRLCLDVPPVPPNAYMPYYLREYVTRLVNGFKPLVSRS
  ARLYRILGVLVHLRIRTREASFEEWLRSKEVALDFGLTERLREHEAQLVILAQALDHYDC
  LIHSTPHTLVERGLQSALKYEEFYLKRFGGHYMESVFQMYTRIAGFLACRATRGMRHIAL
  GREGSWWEMFKFFFHRLYDHQIVPSTPAMLNLGTRNYYTSSCYLVNPQATTNKATLRAIT
  SNVSAILARNGGIGLCVQAFNDSGPGTASVMPALKVLDSLVAAHNKESARPTGACVYLEP
  WHTDVRAVLRMKGVLAGEEAQRCDNIFSALWMPDLFFKRLIRHLDGEKNVTWTLFDRDTS
  MSLADFHGEEFEKLYQHLEVMGFGEQIPIQELAYGIVRSAATTGSPFVMFKDAVNRHYIY
  DTQGAAIAGSNLCTEIVHPASKRSSGVCNLGSVNLARCVSRQTFDFGRLRDAVQACVLMV
  NIMIDSTLQPTPQCTRGNDNLRSMGIGMQGLHTACLKLGLDLESAEFQDLNKHIAEVMLL
  SAMKTSNALCVRGARPFNHFKRSMYRAGRFHWERFPDARPRYEGEWEMLRQSMMKHGLRN
  SQFVALMPTAASAQISDVSEGFAPLFTNLFSKVTRDGETLRPNTLLLKELERTFSGKRLL
  EVMDSLDAKQWSVAQALPCLEPTHPLRRFKTAFDYDQKLLIDLCADRAPYVDHSQSMTLY
  VTEKADGTLPASTLVRLLVHAYKRGLKTGMYYCKVRKATNSGVFGGDDNIVCMSCAL
• 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.
• Reactome Pathway:
  Microbial modulation of RIPK1-mediated regulated necrosis (R-HSA-9686347)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)

Molecular Interaction Atlas (MIA) of This DTT

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BILD-1263	DMUOPBF	Herpes simplex virus infection	1F00	Terminated	[2]
BILD-1351	DMR01WE	Herpes simplex virus infection	1F00	Terminated	[3]
BILD-1357	DMZMUG2	Herpes simplex virus infection	1F00	Terminated	[4]
BILD-733	DMAU5WL	Herpes simplex virus infection	1F00	Terminated	[5]

References

• [1] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [2] 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.
• [3] 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.
• [4] Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity. J Med Chem. 1996 Oct 11;39(21):4173-80.
• [5] 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.