PENCICLOVIR SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H14N5O3.Na
Molecular Weight	275.2396
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].NC1=NC2=C(N=CN2CCC(CO)CO)C(=O)[N-]1

InChI

InChIKey=NMQFQBOIHUIALG-UHFFFAOYSA-M

InChI=1S/C10H15N5O3.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula	C10H14N5O3
Molecular Weight	252.2499
Charge	-1
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
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 19 Target ID: CHEMBL1872 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Inhibitor 8297		16.0 µM [Ki]
DNA polymerase catalytic subunit 14 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 8297		9.5 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Recurrent herpes labialis 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Primary		Approved 8429	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

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 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE2 263 OCT2 647 MATE1 306	aldehyde oxidase 16 esterase 72 CYP 270 OAT2 115 OATP1B1 406 OATP1B3 350 OATP2B1 104 NTCP 17 OCT1 327	OCT2 6 MATE2 5 MATE1 6

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf#page=6 Page: 6.0	no
MATE1 308	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE1 308	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE2 263	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
OCT2 648	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
OCT2 648	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE2 263	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	yes

Drug as victim

Target	Modality	Activity
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-363S-019_review.pdf#page=7 Page: 7.0	no
NTCP 17	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
CYP 270	substrate 3367 Sources: https://pdf.hres.ca/dpd_pm/00029892.PDF#page=13 Page: 13.0	yes
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	yes
aldehyde oxidase 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9224775/	yes
esterase 72	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27298339/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4974	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4974
ChEBI	CHEBI:7956	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7956
ChemicalBook	CB0464901	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0464901
ChemicalBook	CB7731886	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7731886
MolPort	MolPort-003-666-602	https://www.molport.com/shop/molecule-link/MolPort-003-666-602
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	Famciclovir(Famvir)	http://www.selleckchem.com/products/Famciclovir(Famvir).html
Selleck Chemicals	penciclovir	http://www.selleckchem.com/products/penciclovir.html
ZINC	ZINC000000001899	http://zinc15.docking.org/substances/ZINC000000001899
ZINC	ZINC000001530635	http://zinc15.docking.org/substances/ZINC000001530635
eMolecules	32456333	https://www.emolecules.com/cgi-bin/more?vid=32456333
eMolecules	901871	https://www.emolecules.com/cgi-bin/more?vid=901871
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
Selective activity of various antiviral compounds against HHV-7 infection.	1999 Aug	10480261
Evaluation of anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]- guanine (A-5021) in mice.	1999 Jun	10389656
Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicella-zoster virus resistant to acyclovir.	1999 Oct	10508017
Ribavirin and mycophenolic acid potentiate the activity of guanine- and diaminopurine-based nucleoside analogues against hepatitis B virus.	2000 Nov	11114413
Current and potential therapies for the treatment of herpesvirus infections.	2001	11417115
Antiviral drugs: current state of the art.	2001 Aug	11418355
Recurrent herpes labialis: efficacy of topical therapy with penciclovir compared with acyclovir (aciclovir).	2001 Jan	11354919
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
Pharmacokinetic studies of 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyl-oxybut-1-yl)purine, an oral prodrug for the antiviral agent penciclovir.	2001 Jul	11408358
Recent developments in herpesvirus therapy.	2001 Mar	11867011
A review of antiviral therapy for herpes labialis.	2001 Sep	11559222
Viral diseases of the skin: diagnosis and antiviral treatment.	2002	11817982
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
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
Novel agents and strategies to treat herpes simplex virus infections.	2003 Feb	12556212
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
Optimization of cellular nucleotide extraction and sample preparation for nucleotide pool analyses using capillary electrophoresis.	2003 May 5	12668076
In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1.	2004 Apr	15077679
Synthesis and biological evaluation of novel tert-azido or tert-amino substituted penciclovir analogs.	2004 Apr 21	15064793
In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA strain): differences between acyclovir and penciclovir?	2004 Mar	15168799
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	14985094
Characterisation of penciclovir resistant acyclovir sensitive herpes simplex virus type 2 isolated from an AIDS patient.	2004 May	15042649
Topical treatment of herpes labialis.	2004 Nov	15605969
Penciclovir cream--improved topical treatment for herpes simplex infections.	2004 Sep-Oct	15452407
Agents and strategies in development for improved management of herpes simplex virus infection and disease.	2005 Feb	15757392
Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides.	2005 Mar	15728906
Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.	2005 Mar	15728896
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 15 15:30:09 GMT 2023` Edited by `admin` on `Fri Dec 15 15:30:09 GMT 2023`
Record UNII	P06226385L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PENCICLOVIR SODIUM

Official Name

English

PENCICLOVIR SODIUM [ORANGE BOOK]

Common Name

English

6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-(4-HYDROXY-3-(HYDROXYMETHYL)BUTYL)-, SODIUM SALT (1:1)

Systematic Name

English

2-AMINO-1,9-DIHYDRO-9-(4-HYDROXY-3-(HYDROXYMETHYL)BUTYL)-6H-PURIN-6-ONE MONOSODIUM SALT

Common Name

English

9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine monosodium salt

Common Name

English

BRL-39123-D

Code

English

Penciclovir sodium [WHO-DD]

Common Name

English

PENCICLOVIR SODIUM [USAN]

Common Name

English

SODIUM PENCICLOVIR

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29575