Penciclovir

Identification

Summary

Penciclovir is a topical nucleoside polymerase inhibitor used in the treatment of recurrent herpes labialis.

Brand Names
Denavir
Generic Name
Penciclovir
DrugBank Accession Number
DB00299
Background

Penciclovir is a synthetic acyclic guanine derivative with antiviral activity used for the treatment of various herpes simplex virus (HSV) infections. Displaying low toxicity and good selectivity, penciclovir is a nucleoside analogue.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 253.2578
Monoisotopic: 253.117489371
Chemical Formula
C10H15N5O3
Synonyms
  • 9-(4-hydroxy-3-(hydroxymethyl)butyl)guanine
  • 9-(4-hydroxy-3-hydroxymethylbut-1-yl)-guanine
  • 9-[2-hydroxy-1-(hydroxymethyl)-ethoxymethyl]guanine
  • 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]guanine
  • PCV
  • PE2
  • Penciclovir
  • Penciclovirum
External IDs
  • BRL-39123

Pharmacology

Indication

Used to treat recurrent cold sores on the lips and face from various herpesvirus invections.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-1
AThymidine kinase
inducer
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

Adverse Effects
Adverseeffects
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Toxicity

Symptoms of overdose include headache, abdominal pain, increased serum lipase, nausea, dyspepsia, dizziness, and hyperbilirubinemia.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Penciclovir can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Penciclovir can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Penciclovir can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Penciclovir.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Penciclovir.
AcyclovirThe metabolism of Acyclovir can be decreased when combined with Penciclovir.
AdalimumabThe metabolism of Penciclovir can be increased when combined with Adalimumab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Penciclovir.
AgomelatineThe metabolism of Agomelatine can be decreased when combined with Penciclovir.
AlbendazoleThe metabolism of Penciclovir can be increased when combined with Albendazole.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Penciclovir sodiumP06226385L97845-62-0NMQFQBOIHUIALG-UHFFFAOYSA-M
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DenavirCream10 mg/1gTopicalRemedy Repack2014-05-282015-05-28US flag
DenavirCream10 mg/1gTopicalNew American Therapeutics, Inc2010-12-292018-01-31US flag
DenavirCream10 mg/1gTopicalPhysicians Total Care, Inc.2003-11-13Not applicableUS flag
DenavirCream10 mg/1gTopicalPrestium Pharma, Inc.2012-10-232020-02-29US flag
DenavirCream10 mg/1gTopicalRemedy Repack2013-11-182016-11-08US flag
DenavirCream1 %TopicalNovartis2006-08-142013-07-31Canada flag
DenavirCream10 mg/1gTopicalNovartis2009-12-032014-12-31US flag
DenavirCream10 mg/1gTopicalMylan Pharmaceuticals Inc.2018-09-24Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PenciclovirCream10 mg/1gTopicalRenaissance Pharma, Inc.2016-10-012019-07-31US flag

Categories

ATC Codes
D06BB06 — PenciclovirJ05AB13 — Penciclovir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as hypoxanthines. These are compounds containing the purine derivative 1H-purin-6(9H)-one. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Hypoxanthines
Alternative Parents
6-oxopurines / Pyrimidones / Aminopyrimidines and derivatives / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Primary alcohols / Organopnictogen compounds
show 2 more
Substituents
6-oxopurine / Alcohol / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Heteroaromatic compound / Hydrocarbon derivative / Hypoxanthine
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
2-aminopurines, propane-1,3-diols (CHEBI:7956)
Affected organisms
  • Herpes simplex virus

Chemical Identifiers

UNII
359HUE8FJC
CAS number
39809-25-1
InChI Key
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)
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

References

Synthesis Reference
US5075445
General References
  1. FDA Approved Drug Products: DENAVIR (penciclovir) cream [Link]
Human Metabolome Database
HMDB0014444
KEGG Drug
D05407
KEGG Compound
C07417
PubChem Compound
4725
PubChem Substance
46506498
ChemSpider
4563
BindingDB
50210804
RxNav
59839
ChEBI
7956
ChEMBL
CHEMBL1540
ZINC
ZINC000000001899
Therapeutic Targets Database
DAP000488
PharmGKB
PA450839
PDBe Ligand
PE2
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Penciclovir
PDB Entries
1ki3
FDA label
Download (64.7 KB)
MSDS
Download (57.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionCold Sore1
3CompletedTreatmentHerpes Labialis1

Pharmacoeconomics

Manufacturers
  • Novartis consumer health inc
Packagers
  • GlaxoSmithKline Inc.
  • Novartis AG
Dosage Forms
FormRouteStrength
Powder, for solutionIntravenous
CreamTopical1 %
CreamTopical10 mg/1g
CreamTopical
CreamTopical1 g
Prices
Unit descriptionCostUnit
Denavir 1% Cream 1.5 gm Tube53.8USD tube
Denavir 1% cream43.87USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5075445No1991-12-242010-09-24US flag
CA2113080No2003-02-252012-07-03Canada flag
US5840763Yes1998-11-242016-03-01US flag
US5916893Yes1999-06-292016-03-01US flag
US6469015No2002-10-222019-10-22US flag
US6579981No2003-06-172020-06-17US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)275-277 °CNot Available
water solubility1.7mg/mlNot Available
logP-1.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.45 mg/mLALOGPS
logP-0.86ALOGPS
logP-1.5ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)8.01ChemAxon
pKa (Strongest Basic)2.84ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area125.76 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity64.59 m3·mol-1ChemAxon
Polarizability25.11 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9885
Blood Brain Barrier+0.9386
Caco-2 permeable-0.8545
P-glycoprotein substrateSubstrate0.6103
P-glycoprotein inhibitor INon-inhibitor0.9733
P-glycoprotein inhibitor IINon-inhibitor0.9532
Renal organic cation transporterNon-inhibitor0.7342
CYP450 2C9 substrateNon-substrate0.8231
CYP450 2D6 substrateNon-substrate0.7926
CYP450 3A4 substrateNon-substrate0.6681
CYP450 1A2 substrateNon-inhibitor0.8723
CYP450 2C9 inhibitorNon-inhibitor0.935
CYP450 2D6 inhibitorNon-inhibitor0.9398
CYP450 2C19 inhibitorNon-inhibitor0.9323
CYP450 3A4 inhibitorNon-inhibitor0.9713
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9593
Ames testNon AMES toxic0.549
CarcinogenicityNon-carcinogens0.9301
BiodegradationNot ready biodegradable0.9104
Rat acute toxicity2.1426 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8811
hERG inhibition (predictor II)Non-inhibitor0.856
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0190000000-ed1701b795cb216e6d66
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0790000000-212e25de28163f343cac
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0910000000-3a8ca3a0b3701c27b51d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0kai-0900000000-36122e670b73f1113fff
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-053r-1900000000-bceccffce9861527c0c8
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0api-3900000000-2322dab886ffdf508841
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0490000000-0e41d127a3f6d343b9d6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0920000000-8e58b381a6b3d470746b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0900000000-d498bce256e98e4cf88c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0900000000-ae0beed2651e1125764f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0900000000-19ad8b8788d0275996b5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udr-1900000000-5c4ec47a69c82954d428
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0f79-0390000000-2bec5fbdf1e72aa84bde
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0uei-1940000000-6e49677068b47b74940f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-3900000000-cc1f9ce4e3ed563ded5c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0zfr-8900000000-326741cdbb592bb9d271
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0f8c-7900000000-295551b253f3f85729c3
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0udi-0900000000-44a1abcea55a53906b2a

Targets

Drugtargets2
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Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific 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 pro...
Gene Name
Not Available
Uniprot ID
P04293
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
136419.66 Da
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. [Article]
  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. [Article]
  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(9):1111-23. doi: 10.2217/fmb.09.83. [Article]
  4. Deval J: Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66. doi: 10.2165/00003495-200969020-00002. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Not Available
Pharmacological action
Yes
Actions
Inducer
General Function
Thymidine kinase activity
Specific Function
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 the...
Gene Name
TK
Uniprot ID
P06478
Uniprot Name
Thymidine kinase
Molecular Weight
40912.485 Da
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Drug created on June 13, 2005 13:24 / Updated on August 13, 2021 04:43