Identification
NamePenciclovir
Accession NumberDB00299  (APRD00041, DB01730)
TypeSmall Molecule
GroupsApproved
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
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
Penciclovirum
External IDs BRL-39123
Product Ingredients
IngredientUNIICASInChI KeyDetails
Penciclovir sodiumP06226385L 97845-62-0NMQFQBOIHUIALG-UHFFFAOYSA-MDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DenavirCream10 mg/gTopicalPrestium Pharma, Inc.2012-10-23Not applicableUs
DenavirCream10 mg/gTopicalPhysicians Total Care, Inc.2003-11-13Not applicableUs
DenavirCream10 mg/gTopicalRemedy Repack2013-06-112017-11-08Us
DenavirCream10 mg/gTopicalNew American Therapeutics, Inc2010-12-29Not applicableUs
DenavirCream1 %TopicalNovartis2006-08-142013-07-31Canada
DenavirCream10 mg/gTopicalRemedy Repack2014-05-272016-12-16Us
PenciclovirCream10 mg/gTopicalRenaissance Pharma, Inc.2016-10-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII359HUE8FJC
CAS number39809-25-1
WeightAverage: 253.2578
Monoisotopic: 253.117489371
Chemical FormulaC10H15N5O3
InChI KeyJNTOCHDNEULJHD-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
Pharmacology
Indication

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

Structured Indications
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
DNA polymerase catalytic subunitProteinyes
inhibitor
HHV-1P04293 details
Thymidine kinaseProteinyes
inducer
HHV-1P06478 details
Related Articles
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 distributionNot Available
Protein binding

Less than 20%.

Metabolism

Hepatic

Route of eliminationNot Available
Half life

2 hours

ClearanceNot Available
Toxicity

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

Affected organisms
  • Herpes simplex virus
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceUS5075445
General ReferencesNot Available
External Links
ATC CodesD06BB06 — PenciclovirJ05AB13 — Penciclovir
AHFS Codes
  • 84:04.06
PDB Entries
FDA labelDownload (64.7 KB)
MSDSDownload (57.2 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentAdvanced Myeloma / Plasma Cell Myeloma1
2CompletedPreventionMeningococcal Disease1
3CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Streptococcus Pneumoniae1
3CompletedPreventionMeningococcal Disease1
3CompletedPreventionMeningococcal Meningitis / Mumps / Rubella / Rubeola / Varicella1
3CompletedTreatmentHerpes Labialis1
4CompletedPreventionCold Sore1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableRecruitingNot AvailableStreptococcus Pneumoniae1
Pharmacoeconomics
Manufacturers
  • Novartis consumer health inc
Packagers
Dosage forms
FormRouteStrength
CreamTopical1 %
CreamTopical10 mg/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)
CA2113080 No2003-02-252012-07-03Canada
US5075445 No1993-09-242010-09-24Us
US5840763 No1995-09-012015-09-01Us
US5916893 No1995-09-012015-09-01Us
US6469015 No1999-10-222019-10-22Us
US6579981 No2000-06-172020-06-17Us
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0190000000-ed1701b795cb216e6d66View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0790000000-212e25de28163f343cacView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0910000000-3a8ca3a0b3701c27b51dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0kai-0900000000-36122e670b73f1113fffView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-053r-1900000000-bceccffce9861527c0c8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0api-3900000000-2322dab886ffdf508841View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0490000000-0e41d127a3f6d343b9d6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0920000000-8e58b381a6b3d470746bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0900000000-d498bce256e98e4cf88cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0900000000-ae0beed2651e1125764fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0900000000-19ad8b8788d0275996b5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udr-1900000000-5c4ec47a69c82954d428View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0f79-0390000000-2bec5fbdf1e72aa84bdeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0uei-1940000000-6e49677068b47b74940fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-3900000000-cc1f9ce4e3ed563ded5cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0zfr-8900000000-326741cdbb592bb9d271View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0f8c-7900000000-295551b253f3f85729c3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0900000000-44a1abcea55a53906b2aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentHypoxanthines
Alternative Parents6-oxopurines / Pyrimidones / Aminopyrimidines and derivatives / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Primary alcohols / Organopnictogen compounds
Substituents6-oxopurine / Hypoxanthine / Aminopyrimidine / Pyrimidone / N-substituted imidazole / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors2-aminopurines, propane-1,3-diols (CHEBI:7956 )

Targets

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 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. Therefo...
Gene Name:
Not Available
Uniprot ID:
P04293
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. [PubMed:17016423 ]
  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:16033961 ]
  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. [PubMed:19895215 ]
  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. [PubMed:19228073 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
HHV-1
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 their genome.
Gene Name:
TK
Uniprot ID:
P06478
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. [PubMed:17016423 ]
  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:12709344 ]
  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:12959326 ]
  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:17488477 ]
Drug created on June 13, 2005 07:24 / Updated on July 22, 2017 18:04