U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C10H15N5O3
Molecular Weight 253.2578
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PENCICLOVIR

SMILES

NC1=NC2=C(N=CN2CCC(CO)CO)C(=O)N1

InChI

InChIKey=JNTOCHDNEULJHD-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C10H15N5O3
Molecular Weight 253.2578
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/3040998 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2754699

Penciclovir (DENAVIR®) is a synthetic acyclic guanine derivative with antiviral activity, mainly used to treat infections from herpes simplex virus (HSV) types 1 and 2. In cells infected with HSV-1 or HSV-2, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Famciclovir (FAMVIR®) is a prodrug form of penciclovir with improved oral bioavailability.

CNS Activity

Curator's Comment: Known to be CNS penetrant in rats. Human data not available.

Originator

Curator's Comment: Beecham Group plc. is a predecessor of GlaxoSmithKline plc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
16.0 µM [Ki]
Target ID: P89453
Gene ID: 1487316.0
Gene Symbol: NA
Target Organism: Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus|||2)
9.5 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DENAVIR

Approved Use

DENAVIR® is a nucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age and older.

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0 ng/mL
1.8 mg single, topical
dose: 1.8 mg
route of administration: Topical
experiment type: SINGLE
co-administered:
PENCICLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0 ng/mL
1.8 mg 1 times / day steady-state, topical
dose: 1.8 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
PENCICLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.6 μg/mL
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1.6 μg/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.3 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.9 μg/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
17.9 μg × h/mL
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.48 μg × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8.95 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
12.1 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.24 μg × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 % 12 times / day multiple, topical
Recommended
Dose: 1 %, 12 times / day
Route: topical
Route: multiple
Dose: 1 %, 12 times / day
Sources: Page: Study 024
unhealthy, 39
n = 782
Health Status: unhealthy
Condition: Recurrent Herpes Simplex Labialis
Age Group: 39
Sex: M+F
Population Size: 782
Sources: Page: Study 024
Disc. AE: Dissociative disorder...
AEs leading to
discontinuation/dose reduction:
Dissociative disorder
Sources: Page: Study 024
750 mg 3 times / day multiple, oral
MTD
unhealthy
1500 mg single, oral
Recommended
Dose: 1500 mg
Route: oral
Route: single
Dose: 1500 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Herpes labialis
Sources: Page: p.1
Other AEs: Acute renal failure...
AEs

AEs

AESignificanceDosePopulation
Dissociative disorder Disc. AE
1 % 12 times / day multiple, topical
Recommended
Dose: 1 %, 12 times / day
Route: topical
Route: multiple
Dose: 1 %, 12 times / day
Sources: Page: Study 024
unhealthy, 39
n = 782
Health Status: unhealthy
Condition: Recurrent Herpes Simplex Labialis
Age Group: 39
Sex: M+F
Population Size: 782
Sources: Page: Study 024
Acute renal failure
1500 mg single, oral
Recommended
Dose: 1500 mg
Route: oral
Route: single
Dose: 1500 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Herpes labialis
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
In vitro activities of penciclovir and acyclovir against herpes simplex virus types 1 and 2.
1992 Sep
Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells.
2001 May
[Local treatments using antiviral and non-antiviral drugs for herpes facialis and genitalis (excluding pregnant females and neonates at risk)].
2002 Apr
[Genital herpes: epidemiology, transmission, clinic, asymptomatic viral excretion, impact on other sexually transmitted diseases, prevention, and treatment].
2002 Apr
Studies on the thermal decomposition process and kinetics of purine drugs.
2002 Aug
Comparative analysis of DNA breakage, chromosomal aberrations and apoptosis induced by the anti-herpes purine nucleoside analogues aciclovir, ganciclovir and penciclovir.
2002 Aug 29
Antiviral agents: Non-antiretroviral [correction of Nonantiviral] drugs.
2002 Oct
CL1-SR39: A noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography.
2002 Sep
[4'-Thio-5-ethyl-2'-deoxyuridine 5'-phosphonates: synthesis and antiviral activity].
2002 Sep-Oct
MicroPET imaging of prostate cancer in LNCAP-SR39TK-GFP mouse xenografts.
2003 Apr 1
Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis.
2003 Apr 15
Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster.
2003 Aug
Novel agents and strategies to treat herpes simplex virus infections.
2003 Feb
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Herpes simplex virus resistance to antiviral drugs.
2003 Jan
The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis.
2003 Mar
Optimization of cellular nucleotide extraction and sample preparation for nucleotide pool analyses using capillary electrophoresis.
2003 May 5
Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection.
2003 Nov
Profiling penciclovir susceptibility and prevalence of resistance of herpes simplex virus isolates across eleven clinical trials.
2003 Sep
Recurrent herpes simplex labialis: selected therapeutic options.
2003 Sep
Changing paradigms in dermatology: antivirals in dermatology.
2003 Sep-Oct
Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.
2003 Sep-Oct
Inhibition of sickling in vitro by three purine-based antiviral agents: an approach to the treatment of sickle cell disease.
2003 Sep-Oct
In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1.
2004 Apr
Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial.
2004 Apr
Synthesis and biological evaluation of novel tert-azido or tert-amino substituted penciclovir analogs.
2004 Apr 21
Antiviral properties and cytotoxic activity of platinum(II) complexes with 1,10-phenanthrolines and acyclovir or penciclovir.
2004 Aug
Efficacy of antiviral agents in feline herpetic keratitis: results of an in vitro study.
2004 Aug-Sep
Can clinical trials requiring frequent participant contact be conducted over the Internet? Results from an online randomized controlled trial evaluating a topical ointment for herpes labialis.
2004 Feb 17
Therapeutic options for herpes labialis, II: Topical agents.
2004 Jul
Antiviral drugs in current clinical use.
2004 Jun
In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA strain): differences between acyclovir and penciclovir?
2004 Mar
Penciclovir solubility in Eudragit films: a comparison of X-ray, thermal, microscopic and release rate techniques.
2004 Mar 10
Inactivity of the bicyclic pyrimidine nucleoside analogues against simian varicella virus (SVV) does not correlate with their substrate activity for SVV-encoded thymidine kinase.
2004 Mar 19
Characterisation of penciclovir resistant acyclovir sensitive herpes simplex virus type 2 isolated from an AIDS patient.
2004 May
Topical treatment of herpes labialis.
2004 Nov
Recent clinical experience with famciclovir--a "third generation" nucleoside prodrug.
2004 Sep
Penciclovir cream--improved topical treatment for herpes simplex infections.
2004 Sep-Oct
Drugs for non-HIV viral infections.
2005 Apr
Altered deoxyribonucleotide pools in T-lymphoblastoid cells expressing the multisubstrate nucleoside kinase of Drosophila melanogaster.
2005 Aug
Murine cytomegalovirus resistant to antivirals has genetic correlates with human cytomegalovirus.
2005 Aug
Agents and strategies in development for improved management of herpes simplex virus infection and disease.
2005 Feb
Recurrent antiviral-resistant genital herpes in an immunocompetent patient.
2005 Jul 1
Comparison of [14C]FMAU, [3H]FEAU, [14C]FIAU, and [3H]PCV for monitoring reporter gene expression of wild type and mutant herpes simplex virus type 1 thymidine kinase in cell culture.
2005 Jul-Aug
Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides.
2005 Mar
Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.
2005 Mar
Platinum(II) complexes with antitumoral/antiviral aromatic heterocycles: effect of glutathione upon in vitro cell growth inhibition.
2005 May 5
Development and validation of a new reversed-phase ion pairing liquid chromatographic method with fluorescence detection for penciclovir analysis in plasma and aqueous humor.
2005 Nov 5
Clinic-initiated, twice-daily oral famciclovir for treatment of recurrent genital herpes: a randomized, double-blind, controlled trial.
2005 Oct 15
In vitro activity of cycloSal-nucleoside monophosphates and polyhydroxycarboxylates against orthopoxviruses.
2005 Sep
Patents

Sample Use Guides

Penciclovir (DENAVIR®) should be applied every 2 hours during waking hours for a period of 4 days. Treatment should be started as early as possible (i.e., during the prodrome or when lesions appear).
Route of Administration: Topical
In cell culture studies, penciclovir has antiviral activity against the following herpes viruses: HSV-1 and HSV-2. The antiviral activity of penciclovir against wild type strains grown on human foreskin fibroblasts was assessed with a plaque reduction assay and staining with crystal violet 3 days postinfection for HSV. The median EC50 values of penciclovir against laboratory and clinical isolates of HSV-1 and HSV-2 were 2 uM (range 1.2 to 2.4 uM, n=7) and 2.6 uM (range 1.6 to 11 uM, n=6), respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:44:24 GMT 2023
Edited
by admin
on Fri Dec 15 15:44:24 GMT 2023
Record UNII
359HUE8FJC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PENCICLOVIR
INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
PENCICLOVIR [USP IMPURITY]
Common Name English
DENAVIR
Brand Name English
BRL-39123
Code English
NSC-759624
Code English
PENCICLOVIR [VANDF]
Common Name English
PENCICLOVIR [USAN]
Common Name English
9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine
Systematic Name English
PENCICLOVIR [MART.]
Common Name English
2-AMINO-1,9-DIHYDRO-9-(4-HYDROXY-3-(HYDROXYMETHYL)BUTYL)-6H-PURIN-6-ONE
Systematic Name English
Penciclovir [WHO-DD]
Common Name English
penciclovir [INN]
Common Name English
PENCICLOVIR [ORANGE BOOK]
Common Name English
PENCICLOVIR [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AB13
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NDF-RT N0000175468
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NDF-RT N0000175459
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
WHO-VATC QD06BB06
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NDF-RT N0000020060
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NCI_THESAURUS C29575
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NDF-RT N0000175459
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
WHO-VATC QJ05AB13
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
WHO-ATC D06BB06
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NCI_THESAURUS C281
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NDF-RT N0000175459
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
NCI_THESAURUS C1556
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
Code System Code Type Description
DRUG CENTRAL
2079
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
WIKIPEDIA
PENCICLOVIR
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
EVMPD
SUB09661MIG
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
DRUG BANK
DB00299
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
NCI_THESAURUS
C66337
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
RXCUI
59839
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY RxNorm
NSC
759624
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
INN
6437
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
CHEBI
7956
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
SMS_ID
100000091073
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
ChEMBL
CHEMBL1540
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
HSDB
8123
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
USAN
EE-83
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
MERCK INDEX
m8462
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY Merck Index
FDA UNII
359HUE8FJC
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
LACTMED
Penciclovir
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
CAS
39809-25-1
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
DAILYMED
359HUE8FJC
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
EPA CompTox
DTXSID9046491
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
MESH
C053539
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
PUBCHEM
135398748
Created by admin on Fri Dec 15 15:44:24 GMT 2023 , Edited by admin on Fri Dec 15 15:44:24 GMT 2023
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
The in vitro activities of penciclovir against HSV-1, HSV-2 and VZV are similar to those of aciclovir, with median IC50 values of 0.4, 1.5 and 4.0 µg/mL, respectively, in MRC-5 cells.
IC50
TARGET ORGANISM->INHIBITOR
The in vitro activities of penciclovir against HSV-1, HSV-2 and VZV are similar to those of aciclovir, with median IC50 values of 0.4, 1.5 and 4.0 µg/mL, respectively, in MRC-5 cells.
IC50
TARGET ORGANISM->INHIBITOR
The in vitro activities of penciclovir against HSV-1, HSV-2 and VZV are similar to those of aciclovir, with median IC50 values of 0.4, 1.5 and 4.0 µg/mL, respectively, in MRC-5 cells.
IC50
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
METABOLITE INACTIVE -> PARENT
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY