PENCICLOVIR

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human herpesvirus 1 DNA polymerase 17 Target ID: CHEMBL1872 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Inhibitor 8146		16.0 µM [Ki]
DNA polymerase catalytic subunit 12 Target ID: P89453 Gene ID: 1487316.0 Gene Symbol: NA Target Organism: Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus\|\|\|2) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Inhibitor 8146		9.5 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Recurrent herpes labialis 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Primary		Approved 8307	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 8.4352323E11

C_max

Value	Dose	Analyte	Population
0 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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

Value	Dose	Analyte	Population
17.9 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	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

Dose	Population	Adverse events
1 % 12 times / day multiple, topical Recommended Dose: 1 %, 12 times / day Route: topical Route: multiple Dose: 1 %, 12 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024	Disc. AE: Dissociative disorder... AEs leading to discontinuation/dose reduction: Dissociative disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024
750 mg 3 times / day multiple, oral MTD Dose: 750 mg, 3 times / day Route: oral Route: multiple Dose: 750 mg, 3 times / day Sources: https://www.medsafe.govt.nz/Profs/Datasheet/a/APOHEALTHFamciclovirOncetab.pdf https://www.ema.europa.eu/en/documents/referral/famvir-article-30-referral-assessment-report_en.pdf	unhealthy Health Status: unhealthy Condition: Herpes zoster Sources: https://www.medsafe.govt.nz/Profs/Datasheet/a/APOHEALTHFamciclovirOncetab.pdf https://www.ema.europa.eu/en/documents/referral/famvir-article-30-referral-assessment-report_en.pdf	Sources: https://www.medsafe.govt.nz/Profs/Datasheet/a/APOHEALTHFamciclovirOncetab.pdf https://www.ema.europa.eu/en/documents/referral/famvir-article-30-referral-assessment-report_en.pdf
1500 mg single, oral Recommended Dose: 1500 mg Route: oral Route: single Dose: 1500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Herpes labialis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1	Other AEs: Acute renal failure... Other AEs: Acute renal failure Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024
Acute renal failure		1500 mg single, oral Recommended Dose: 1500 mg Route: oral Route: single Dose: 1500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Herpes labialis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1532

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE2 259 OCT2 630 MATE1 302	aldehyde oxidase 15 esterase 68 CYP 252 OAT2 111 OATP1B1 389 OATP1B3 333 OATP2B1 103 NTCP 16 OCT1 317	OCT2 5 MATE2 4 MATE1 5

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1857	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf#page=6 Page: 6.0	no
MATE1 304	inducer 1515 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE1 304	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE2 259	inducer 1515 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
OCT2 631	inducer 1515 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
OCT2 631	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE2 259	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	yes

Drug as victim

Target	Modality	Activity
CYP 252	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-363S-019_review.pdf#page=7 Page: 7.0	no
NTCP 16	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP1B1 389	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP1B3 333	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP2B1 103	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OCT1 317	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
CYP 252	substrate 3264 Sources: https://pdf.hres.ca/dpd_pm/00029892.PDF#page=13 Page: 13.0	yes
OAT2 111	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	yes
aldehyde oxidase 15	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/9224775/	yes
esterase 68	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/27298339/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7956	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7956
ChemicalBook	CB7731886	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7731886
MolPort	MolPort-003-849-798	https://www.molport.com/shop/molecule-link/MolPort-003-849-798
MolPort	MolPort-006-167-513	https://www.molport.com/shop/molecule-link/MolPort-006-167-513
Selleck Chemicals	penciclovir	http://www.selleckchem.com/products/penciclovir.html
ZINC	ZINC000000001899	http://zinc15.docking.org/substances/ZINC000000001899
eMolecules	32456333	https://www.emolecules.com/cgi-bin/more?vid=32456333
eMolecules	902282	https://www.emolecules.com/cgi-bin/more?vid=902282

PubMed

Title	Date	PubMed
In vitro activities of penciclovir and acyclovir against herpes simplex virus types 1 and 2.	1992 Sep	1329640
Guanosine analogues as anti-herpesvirus agents.	2000 Oct-Dec	11200257
Current and potential therapies for the treatment of herpesvirus infections.	2001	11417115
Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents.	2001 Apr-Jul	11563039
Antiviral drugs: current state of the art.	2001 Aug	11418355
Topical treatment of recurrent herpes labialis.	2001 Jan	11354913
8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET.	2001 Jan	11197989
Recent developments in herpesvirus therapy.	2001 Mar	11867011
Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells.	2001 May	12959326
Penciclovir for the treatment of herpes simplex labialis: a review.	2001 May-Jun	11693011
Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET.	2001 Nov	11696640
Novel 5-vinyl pyrimidine nucleosides with potent anti-hepatitis B virus activity.	2001 Nov 19	11677126
Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8.	2001 Nov-Dec	11747000
A review of antiviral therapy for herpes labialis.	2001 Sep	11559222
Comparison of new topical treatments for herpes labialis: efficacy of penciclovir cream, acyclovir cream, and n-docosanol cream against experimental cutaneous herpes simplex virus type 1 infection.	2001 Sep	11559210
[Local treatments using antiviral and non-antiviral drugs for herpes facialis and genitalis (excluding pregnant females and neonates at risk)].	2002 Apr	12122334
Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues.	2002 Apr	11879697
Comparative analysis of DNA breakage, chromosomal aberrations and apoptosis induced by the anti-herpes purine nucleoside analogues aciclovir, ganciclovir and penciclovir.	2002 Aug 29	12175901
New treatments for genital herpes.	2002 Feb	11964906
Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled trial.	2002 Jun	12060504
Effective treatment of herpes simplex labialis with penciclovir cream: combined results of two trials.	2002 Mar	11934185
The A167Y mutation converts the herpes simplex virus type 1 thymidine kinase into a guanosine analogue kinase.	2002 May 21	12009916
Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations.	2002 May 7	12019036
Antiviral agents: Non-antiretroviral [correction of Nonantiviral] drugs.	2002 Oct	12271305
CL1-SR39: A noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography.	2002 Sep	12187266
Current and potential therapies for the treatment of herpes-virus infections.	2003	12790345
Molecular imaging of protein-protein interactions: controlled expression of p53 and large T-antigen fusion proteins in vivo.	2003 Apr 15	12702563
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	12696003
Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster.	2003 Aug	15482124
Generation of stable cell lines expressing Lamivudine-resistant hepatitis B virus for antiviral-compound screening.	2003 Jun	12760870
The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis.	2003 Mar	12653734
Brivudine: a herpes virostatic with rapid antiviral activity and once-daily dosing.	2003 May	12861349
Recurrent herpes simplex labialis: selected therapeutic options.	2003 Sep	12954137
Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.	2003 Sep-Oct	14505192
Inhibition of sickling in vitro by three purine-based antiviral agents: an approach to the treatment of sickle cell disease.	2003 Sep-Oct	12972037
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	15018852
Antiviral properties and cytotoxic activity of platinum(II) complexes with 1,10-phenanthrolines and acyclovir or penciclovir.	2004 Aug	15271515
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	15111272
Therapeutic options for herpes labialis, II: Topical agents.	2004 Jul	15293698
Antiviral drugs in current clinical use.	2004 Jun	15125867
In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA strain): differences between acyclovir and penciclovir?	2004 Mar	15168799
Recent clinical experience with famciclovir--a "third generation" nucleoside prodrug.	2004 Sep	15535046
Penciclovir cream--improved topical treatment for herpes simplex infections.	2004 Sep-Oct	15452407
Altered deoxyribonucleotide pools in T-lymphoblastoid cells expressing the multisubstrate nucleoside kinase of Drosophila melanogaster.	2005 Aug	16045762
Murine cytomegalovirus resistant to antivirals has genetic correlates with human cytomegalovirus.	2005 Aug	16033961
Recurrent antiviral-resistant genital herpes in an immunocompetent patient.	2005 Jul 1	15942905
Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides.	2005 Mar	15728906
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	16140045
Clinic-initiated, twice-daily oral famciclovir for treatment of recurrent genital herpes: a randomized, double-blind, controlled trial.	2005 Oct 15	16163627
In vitro activity of cycloSal-nucleoside monophosphates and polyhydroxycarboxylates against orthopoxviruses.	2005 Sep	16076502

Patents

Sample Use Guides

In Vivo Use Guide

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 Vitro Use Guide

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 16 18:01:35 UTC 2022` Edited by `admin` on `Fri Dec 16 18:01:35 UTC 2022`
Record UNII	359HUE8FJC
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PENCICLOVIR

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