FAMCICLOVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H19N5O4
Molecular Weight	321.3318
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC(=O)OCC(CCN1C=NC2=CN=C(N)N=C12)COC(C)=O

InChI

InChIKey=GGXKWVWZWMLJEH-UHFFFAOYSA-N

InChI=1S/C14H19N5O4/c1-9(20)22-6-11(7-23-10(2)21)3-4-19-8-17-12-5-16-14(15)18-13(12)19/h5,8,11H,3-4,6-7H2,1-2H3,(H2,15,16,18)

HIDE SMILES / InChI

Molecular Formula	C14H19N5O4
Molecular Weight	321.3318
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Inhibitor 8,297		16.0 µM [Ki]
DNA polymerase catalytic subunit 14	Inhibitor 8,297		9.5 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Recurrent herpes labialis 3	Primary		Approved 8,429	DENAVIR

C_max

Value	Dose	Analyte	Population
0 ng/mL	1.8 mg single, topical	PENCICLOVIR plasma	Homo sapiens
0 ng/mL	1.8 mg 1 times / day steady-state, topical	PENCICLOVIR plasma	Homo sapiens
6.6 μg/mL	1000 mg single, oral	PENCICLOVIR unknown	Homo sapiens
1.6 μg/mL	250 mg single, oral	PENCICLOVIR unknown	Homo sapiens
3.3 μg/mL	500 mg single, oral	PENCICLOVIR unknown	Homo sapiens
4 μg/mL	500 mg single, oral	PENCICLOVIR unknown	Homo sapiens
0.9 μg/mL	125 mg single, oral	PENCICLOVIR unknown	Homo sapiens

AUC

Value	Dose	Analyte	Population
17.9 μg × h/mL	1000 mg single, oral	PENCICLOVIR unknown	Homo sapiens
4.48 μg × h/mL	250 mg single, oral	PENCICLOVIR unknown	Homo sapiens
8.95 μg × h/mL	500 mg single, oral	PENCICLOVIR unknown	Homo sapiens
12.1 μg × h/mL	500 mg single, oral	PENCICLOVIR unknown	Homo sapiens
2.24 μg × h/mL	125 mg single, oral	PENCICLOVIR unknown	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.3 h	500 mg single, oral		PENCICLOVIR unknown	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1 % 12 times / day multiple, topical Recommended	unhealthy, 39 n = 782	Disc. AE: Dissociative disorder...
750 mg 3 times / day multiple, oral MTD	unhealthy
1500 mg single, oral Recommended	unhealthy	Other AEs: Acute renal failure...

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AEs

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AE	Significance	Dose	Population
Dissociative disorder	Disc. AE	1 % 12 times / day multiple, topical Recommended	unhealthy, 39 n = 782
Acute renal failure		1500 mg single, oral Recommended	unhealthy

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587

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

Show entries

Target	Modality	Activity
CYP3A4 1,925	inhibitor 3,277	no
MATE1 308	inducer 1,573	no
MATE1 308	inhibitor 3,277	no
MATE2 263	inducer 1,573	no
OCT2 648	inducer 1,573	no

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Drug as victim

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Target	Modality	Activity
CYP 270	substrate 3,367	no
NTCP 17	substrate 3,367	no
OATP1B1 406	substrate 3,367	no
OATP1B3 350	substrate 3,367	no
OATP2B1 104	substrate 3,367	no

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Sourcing

Sourcing

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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

Showing 1 to 5 of 14 entries

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PubMed

Show entries

Title	Date	PubMed
Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs.	1999 Dec	10582877
Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B virus activity in cell culture.	2000 Jan	10718947
Ribavirin and mycophenolic acid potentiate the activity of guanine- and diaminopurine-based nucleoside analogues against hepatitis B virus.	2000 Nov	11114413
Guanosine analogues as anti-herpesvirus agents.	2000 Oct-Dec	11200257
Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice.	2001	11749671

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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.