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
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 Key
Penciclovir sodiumP06226385L97845-62-0NMQFQBOIHUIALG-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DenavirCream10 mg/gTopicalPrestium Pharma, Inc.2012-10-23Not applicableUs
DenavirCream10 mg/gTopicalRemedy Repack2013-06-112017-11-08Us
DenavirCream10 mg/gTopicalRemedy Repack2014-05-272016-12-16Us
DenavirCream1 %TopicalNovartis2006-08-142013-07-31Canada
DenavirCream10 mg/gTopicalNew American Therapeutics, Inc2010-12-29Not applicableUs
DenavirCream10 mg/gTopicalMylan Pharmaceuticals2018-07-11Not applicableUs
DenavirCream10 mg/gTopicalPhysicians Total Care, Inc.2003-11-13Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PenciclovirCream10 mg/gTopicalRenaissance Pharma, Inc.2016-10-01Not applicableUs
Categories
UNII
359HUE8FJC
CAS number
39809-25-1
Weight
Average: 253.2578
Monoisotopic: 253.117489371
Chemical Formula
C10H15N5O3
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

Pharmacology

Indication

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

Associated Conditions
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
HHV-1
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AdalimumabThe serum concentration of Penciclovir can be decreased when it is combined with Adalimumab.Approved
AdenosineThe therapeutic efficacy of Adenosine can be decreased when used in combination with Penciclovir.Approved, Investigational
BenzphetamineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with Penciclovir.Approved, Illicit
CarbamazepineThe serum concentration of Penciclovir can be decreased when it is combined with Carbamazepine.Approved, Investigational
CimetidineThe metabolism of Penciclovir can be decreased when combined with Cimetidine.Approved, Investigational
CiprofloxacinThe serum concentration of Penciclovir can be increased when it is combined with Ciprofloxacin.Approved, Investigational
DiethylpropionThe risk or severity of adverse effects can be increased when Diethylpropion is combined with Penciclovir.Approved, Illicit
EstradiolThe serum concentration of Penciclovir can be increased when it is combined with Estradiol.Approved, Investigational, Vet Approved
Ethinyl EstradiolThe serum concentration of Penciclovir can be increased when it is combined with Ethinyl Estradiol.Approved
EthosuximideEthosuximide may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved
EverolimusThe metabolism of Penciclovir can be decreased when combined with Everolimus.Approved
FlunarizineFlunarizine may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved
FluvoxamineThe metabolism of Penciclovir can be decreased when combined with Fluvoxamine.Approved, Investigational
GabapentinGabapentin may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Investigational
Interferon alfa-n3The metabolism of Penciclovir can be decreased when combined with Interferon alfa-n3.Approved, Investigational
Interferon beta-1aThe metabolism of Penciclovir can be decreased when combined with Interferon beta-1a.Approved, Investigational
Interferon gamma-1bThe metabolism of Penciclovir can be decreased when combined with Interferon gamma-1b.Approved, Investigational
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Penciclovir.Approved
LamotrigineLamotrigine may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Investigational
LevetiracetamLevetiracetam may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Investigational
Magnesium sulfateMagnesium sulfate may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Investigational, Vet Approved
MethimazoleThe serum concentration of Penciclovir can be increased when it is combined with Methimazole.Approved
MethsuximideMethsuximide may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved
MetoprololThe risk or severity of adverse effects can be increased when Metoprolol is combined with Penciclovir.Approved, Investigational
MoxifloxacinThe metabolism of Penciclovir can be decreased when combined with Moxifloxacin.Approved, Investigational
NylidrinThe risk or severity of adverse effects can be increased when Nylidrin is combined with Penciclovir.Approved
NystatinThe metabolism of Penciclovir can be decreased when combined with Nystatin.Approved, Vet Approved
OxymetazolineThe risk or severity of adverse effects can be increased when Oxymetazoline is combined with Penciclovir.Approved, Investigational
Peginterferon alfa-2aThe metabolism of Penciclovir can be decreased when combined with Peginterferon alfa-2a.Approved, Investigational
Peginterferon alfa-2bThe metabolism of Penciclovir can be decreased when combined with Peginterferon alfa-2b.Approved
PhenobarbitalThe serum concentration of Penciclovir can be decreased when it is combined with Phenobarbital.Approved, Investigational
PhenylephrineThe risk or severity of adverse effects can be increased when Phenylephrine is combined with Penciclovir.Approved
PregabalinPregabalin may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Illicit, Investigational
PropafenoneThe serum concentration of Penciclovir can be increased when it is combined with Propafenone.Approved
PropranololThe risk or severity of adverse effects can be increased when Propranolol is combined with Penciclovir.Approved, Investigational
PseudoephedrineThe risk or severity of adverse effects can be increased when Pseudoephedrine is combined with Penciclovir.Approved
TopiramateTopiramate may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved
TrimethadioneTrimethadione may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved
Valproic AcidValproic Acid may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Investigational
VinpocetineVinpocetine may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Investigational
ZonisamideZonisamide may increase the excretion rate of Penciclovir which could result in a lower serum level and potentially a reduction in efficacy.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference
US5075445
General References
Not Available
External Links
Human Metabolome Database
HMDB0014444
KEGG Drug
D05407
KEGG Compound
C07417
PubChem Compound
4725
PubChem Substance
46506498
ChemSpider
4563
BindingDB
50210804
ChEBI
7956
ChEMBL
CHEMBL1540
Therapeutic Targets Database
DAP000488
PharmGKB
PA450839
HET
PE2
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Penciclovir
ATC Codes
R03DA20 — Combinations of xanthinesD06BB06 — PenciclovirJ05AB13 — Penciclovir
PDB Entries
1ki3
FDA label
Download (64.7 KB)
MSDS
Download (57.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentBladder Cancers / Colorectal Cancers / Head and Neck Carcinoma / Lung Cancer Non-Small Cell Cancer (NSCLC) / Melanoma / Other Solid Cancers / Renal Cancers / Triple Negative Breast Cancer (TNBC) / Tumors1
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
  • GlaxoSmithKline Inc.
  • Novartis AG
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)
US5075445No1993-09-242010-09-24Us
CA2113080No2003-02-252012-07-03Canada
US5840763Yes1996-03-012016-03-01Us
US5916893Yes1996-03-012016-03-01Us
US6469015No1999-10-222019-10-22Us
US6579981No2000-06-172020-06-17Us

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

Taxonomy

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 / Hypoxanthine / Aminopyrimidine / Pyrimidone / N-substituted imidazole / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
2-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 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. [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 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. [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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da

Drug created on June 13, 2005 07:24 / Updated on August 15, 2018 14:28