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Identification
Name Penciclovir
Accession Number DB00299 (APRD00041, DB01730)
Type small molecule
Groups approved
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 Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • PE2
  • Penciclovirum [INN-Latin]
Brand names
  • Denavir
Brand name mixtures Not Available
Categories
  • Antiviral Agents
CAS number 39809-25-1
Weight Average: 253.2578
Monoisotopic: 253.117489371
Chemical Formula C10H15N5O3
InChI Key InChIKey=JNTOCHDNEULJHD-UHFFFAOYSA-N
InChI
InChI=1S/C10H15N5O3/c11-10-13-8-7(9(18)14-10)12-5-15(8)2-1-6(3-16)4-17/h5-6,16-17H,1-4H2,(H3,11,13,14,18)
Plain Text
IUPAC Name
2-amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-6,9-dihydro-3H-purin-6-one
SMILES
NC1=NC(=O)C2=C(N1)N(CCC(CO)CO)C=N2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Hypoxanthines
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
  • Hypoxanthines
Pharmacology
Indication Used to treat recurrent cold sores on the lips and face from various herpesvirus invections.
Pharmacodynamics Penciclovir is the active metabolite of the oral product famciclovir. The more favorable results observed with topical penciclovir versus topical acyclovir for the treatment of herpes labialis may be due to the longer intracellular half-life of penciclovir in HSV-infected cells. The activated drug inhibits the viral DNA polymerase. This impairs the ability of the virus to replicate within the cell.
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.
Volume of distribution Not Available
Protein binding Less than 20%.
Metabolism

Hepatic
Route of elimination Not Available
Half life 2 hours
Clearance Not Available
Toxicity Symptoms of overdose include headache, abdominal pain, increased serum lipase, nausea, dyspepsia, dizziness, and hyperbilirubinemia.
Affected organisms
  • Herpes simplex virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis consumer health inc
Packagers
Dosage forms
Form Route Strength
Cream Topical
Prices
Unit description Cost Unit
Denavir 1% Cream 1.5 gm Tube 53.8 USD tube
Denavir 1% cream 43.87 USD g
Patents
Country Patent Number Approved Expires
United States 6579981 2000-06-17 2020-06-17
United States 5075445 1993-09-24 2010-09-24
Canada 2113080 2003-02-25 2012-07-03
Properties
State solid
Melting point 275-277 oC
Experimental Properties
Property Value Source
water solubility 1.7mg/ml PhysProp
logP -1.1 PhysProp
Predicted Properties
Property Value Source
water solubility 7.45e+00 g/l ALOGPS
logP -0.86 ALOGPS
logP -1.55 ChemAxon Molconvert
logS -1.53 ALOGPS
pKa 15.10 ChemAxon Molconvert
hydrogen acceptor count 7 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 125.76 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 64.59 ChemAxon Molconvert
polarizability 25.11 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D05407 Link_out
KEGG Compound C07417 Link_out
PubChem Compound 4725 Link_out
PubChem Substance 46506498 Link_out
ChemSpider 4563 Link_out
ChEBI 7956 Link_out
ChEMBL 7956 Link_out
Therapeutic Targets Database DAP000488 Link_out
PharmGKB PA450839 Link_out
HET PE2 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/penciclovir.htm Link_out
Drugs.com http://www.drugs.com/cdi/penciclovir.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Penciclovir Link_out
ATC Codes
  • D06BB06
  • J05AB13
AHFS Codes
  • 84:04.06
PDB Entries
FDA label show (64.7 KB)
MSDS show (57.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P04293 Link_out
Gene: UL30
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. Deval J: Antimicrobial strategies: inhibition of viral polymerases by 3’-hydroxyl nucleosides. Drugs. 2009;69(2):151-66. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Thymidine kinase

Pharmacological action: yes
Actions: inducer

In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome

Organism class: viral
UniProt ID: P06478 Link_out
Gene: TK
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on October 11, 2011 15:55

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.