DT-Web

DB00299 - Penciclovir


Identification
Name Penciclovir
Accession Number DB00299 (APRD00041, DB01730)
Type small molecule
Description Penciclovir is a guanine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. [Wikipedia]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 253.2578
Groups approved
Monoisotopic Weight 253.117489371
Pharmacology
Indication Used to treat recurrent cold sores on the lips and face from various herpesvirus invections.
Mechanism of action Penciclovir has in vitro activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). In cells infected with HSV-1 or HSV-2, viral thymidine kinase phosphorylates penciclovir to a monophosphate form. The monophosphate form of the drug is then converted to penciclovir triphosphate by cellular kinases. The intracellular triphosphate of penciclovir is retained in vitro inside HSV-infected cells for 10-20 hours, compared with 0.7-1 hour for acyclovir. in vitro studies show that penciclovir triphosphate selectively inhibits viral DNA polymerase by competing with deoxyguanosine triphosphate. Inhibition of DNA synthesis of virus-infected cells inhibits viral replication. In cells not infected with HSV, DNA synthesis is unaltered. Resistant mutants of HSV can occur from qualitative changes in viral thymidine kinase or DNA polymerase. The most commonly encountered acyclovir-resistant mutants that are deficient in viral thymidine kinase are also resistant to penciclovir.
Absorption Measurable penciclovir concentrations were not detected in plasma or urine of healthy male volunteers (n= 12) following single or repeat application of the 1% cream at a dose of 180 mg penciclovir daily.
Protein binding Less than 20%.
Biotransformation Hepatic
Route of elimination Not Available
Toxicity Symptoms of overdose include headache, abdominal pain, increased serum lipase, nausea, dyspepsia, dizziness, and hyperbilirubinemia.
Affected organisms
  • Herpes simplex virus
Interactions
Drug Interactions
Drug Mechanism of interaction
Aluminium The multivalent agent decreases the effect of penicillamine
Attapulgite The multivalent agent decreases the effect of penicillamine
Digoxin The multivalent agent decreases the effect of penicillamine
Iron The multivalent agent decreases the effect of penicillamine
Kaolin The multivalent agent decreases the effect of penicillamine
Food Interactions Not Available

Targets


DNA polymerase
Name DNA polymerase
Gene Name UL30
Pharmacological action yes
Actions inhibitor
References
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Scott GM, Ng HL, Morton CJ, Parker MW, Rawlinson WD: Murine cytomegalovirus resistant to antivirals has genetic correlates with human cytomegalovirus. J Gen Virol. 2005 Aug;86(Pt 8):2141-51. - Pubmed
  • Agut H, Boutolleau D, Deback C, Bonnafous P, Gautheret-Dejean A: Testing the susceptibility of human herpesviruses to antivirals. Future Microbiol. 2009 Nov;4:1111-23. - Pubmed
  • Deval J: Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.8558
Thymidine kinase
Name Thymidine kinase
Gene Name TK
Pharmacological action yes
Actions inducer
References
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Suzutani T, Ishioka K, De Clercq E, Ishibashi K, Kaneko H, Kira T, Hashimoto K, Ogasawara M, Ohtani K, Wakamiya N, Saijo M: Differential mutation patterns in thymidine kinase and DNA polymerase genes of herpes simplex virus type 1 clones passaged in the presence of acyclovir or penciclovir. Antimicrob Agents Chemother. 2003 May;47(5):1707-13. - Pubmed
  • Shaw MM, Gurr WK, Watts PA, Littler E, Field HJ: Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells. Antivir Chem Chemother. 2001 May;12(3):175-86. - Pubmed
  • Shaw MM, Gurr WK, McCrimmon RJ, Schorderet DF, Sherwin RS: 5'AMP-activated protein kinase alpha deficiency enhances stress-induced apoptosis in BHK and PC12 cells. J Cell Mol Med. 2007 Mar-Apr;11(2):286-98. - Pubmed
DTHybrid score 0.0306

Predictions


Id Partner name Gene Name Score
379 DNA polymerase UL54 0.8558
697 DNA polymerase ORF28 0.8558
2482 DNA polymerase 43 0.8558
4104 DNA polymerase BALF5 0.8558
1729 Solute carrier family 22 member 6 SLC22A6 0.0664
6142 Solute carrier family 22 member 8 SLC22A8 0.0448
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.044
6020 Aldehyde oxidase AOX1 0.0392
738 Monocarboxylate transporter 1 SLC16A1 0.0333
6145 Solute carrier family 22 member 1 SLC22A1 0.0315
509 Thymidine kinase TK 0.0306
2559 Thymidine kinase TK 0.0306
3430 Thymidine kinase tdk 0.0306
3518 Thymidine kinase TK 0.0306
5301 Thymidine kinase tdk 0.0306
5771 Thymidine kinase ORF36 0.0306
7009 Thymidine kinase ORF36 0.0306
471 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) SLC6A14 0.027
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0228
6143 Solute carrier family 22 member 7 SLC22A7 0.0206
4512 Cytochrome P450 3A4 CYP3A4 0.0178
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0149
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0143
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