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

Details

Stereochemistry ABSOLUTE
Molecular Formula C13H20N6O4
Molecular Weight 324.3362
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VALACYCLOVIR

SMILES

CC(C)[C@@]([H])(C(=O)OCCOCn1cnc2c1[nH]c(=N)nc2O)N

InChI

InChIKey=HDOVUKNUBWVHOX-QMMMGPOBSA-N
InChI=1S/C13H20N6O4/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20)/t8-/m0/s1

HIDE SMILES / InChI

Molecular Formula C13H20N6O4
Molecular Weight 324.3362
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT01682109 | https://www.ncbi.nlm.nih.gov/pubmed/19957998 | https://www.ncbi.nlm.nih.gov/pubmed/7625798 | https://www.ncbi.nlm.nih.gov/pubmed/11454935

Valacyclovir is the hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir. Valacyclovir is a nucleoside analog DNA polymerase inhibitor. Valacyclovir hydrochloride is rapidly converted to acyclovir which has demonstrated antiviral activity against HSV types 1 (HSV-1) and 2 (HSV-2) and VZV both in cell culture and in vivo. The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analog. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In biochemical assays, acyclovir triphosphate inhibits replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK. The resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of VZV with reduced susceptibility to acyclovir have been recovered from patients with AIDS. Valaciclovir is indicated for the treatment of HSV and VZV infections, including Oral and genital herpes simplex (treatment and prophylaxis), Reduction of HSV transmission from people with recurrent infection to uninfected individuals, Prevention of cytomegalovirus following organ transplantation, Prophylaxis against herpesviruses in immunocompromised patients (such as patients undergoing cancer chemotherapy). Common adverse drug reactions (≥1% of patients) associated with valaciclovir therapy are the same as for aciclovir, its active metabolite, and include nausea, vomiting, diarrhea, and headache. Infrequent adverse effects (0.1–1% of patients) include agitation, vertigo, confusion, dizziness, edema, arthralgia, sore throat, constipation, abdominal pain, rash, weakness and/or renal impairment. Rare adverse effects (<0.1% of patients) include coma, seizures, neutropenia, leukopenia, tremor, ataxia, encephalopathy, psychotic symptoms, crystalluria, anorexia, fatigue, hepatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and/or anaphylaxis.

CNS Activity

Curator's Comment:: Valacyclovir hydrochloride is rapidly converted to acyclovir which was detected in CSF after oral administration of valacyclovir.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZOVIRAX

Approved Use

Oral ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Zoster Infections: ZOVIRAX is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: ZOVIRAX is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox: ZOVIRAX is indicated for the treatment of chickenpox (varicella). Injectable ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Simplex Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients. Initial Episodes of Herpes Genitalis: ZOVIRAX for Injection is indicated for the treatment of severe initial clinical episodes of herpes genitalis in immunocompetent patients. Herpes Simplex Encephalitis: ZOVIRAX for Injection is indicated for the treatment of herpessimplex encephalitis. Neonatal Herpes Simplex Virus Infection: ZOVIRAX for Injection is indicated for the treatmentof neonatal herpes infections. Varicella-Zoster Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of varicella-zoster (shingles) infections in immunocompromised patients.

Launch Date

3.86208006E11
Primary
ZOVIRAX

Approved Use

Oral ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Zoster Infections: ZOVIRAX is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: ZOVIRAX is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox: ZOVIRAX is indicated for the treatment of chickenpox (varicella). Injectable ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Simplex Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients. Initial Episodes of Herpes Genitalis: ZOVIRAX for Injection is indicated for the treatment of severe initial clinical episodes of herpes genitalis in immunocompetent patients. Herpes Simplex Encephalitis: ZOVIRAX for Injection is indicated for the treatment of herpessimplex encephalitis. Neonatal Herpes Simplex Virus Infection: ZOVIRAX for Injection is indicated for the treatmentof neonatal herpes infections. Varicella-Zoster Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of varicella-zoster (shingles) infections in immunocompromised patients.

Launch Date

3.86208006E11
Primary
VALTREX

Approved Use

INDICATIONS AND USAGE. VALTREX is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients Cold Sores (Herpes Labialis), Genital Herpes, Treatment in immunocompetent patients (initial or recurrent episode), Suppression in immunocompetent or HIV-infected patients, Reduction of transmission, Herpes Zoster. Pediatric Patients Cold Sores (Herpes Labialis), Chickenpox Limitations of Use. The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Launch Date

1.07896321E12
Primary
VALTREX

Approved Use

INDICATIONS AND USAGE. VALTREX is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients Cold Sores (Herpes Labialis), Genital Herpes, Treatment in immunocompetent patients (initial or recurrent episode), Suppression in immunocompetent or HIV-infected patients, Reduction of transmission, Herpes Zoster. Pediatric Patients Cold Sores (Herpes Labialis), Chickenpox Limitations of Use. The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Launch Date

1.07887683E12
Primary
VALTRE

Approved Use

INDICATIONS AND USAGE. VALTREX is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients Cold Sores (Herpes Labialis), Genital Herpes, Treatment in immunocompetent patients (initial or recurrent episode), Suppression in immunocompetent or HIV-infected patients, Reduction of transmission, Herpes Zoster. Pediatric Patients Cold Sores (Herpes Labialis), Chickenpox Limitations of Use. The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Launch Date

1.07887683E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
599.2 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACYCLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3015.7 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACYCLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.9 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACYCLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
79%
ACYCLOVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
The S-acyl-2-thioethyl pronucleotide approach applied to acyclovir: part I. Synthesis and in vitro anti-hepatitis B virus activity of bis(S-acyl-2-thioethyl)phosphotriester derivatives of acyclovir.
1999 Jan
Nucleosides and nucleotides. 185. Synthesis and biological activities of 4'alpha-C-branched-chain sugar pyrimidine nucleosides.
1999 Jul 29
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
[Cerebral and renal toxicity of acyclovir in a patient treated for meningoencephalitis].
1999 Nov
Synthesis and antiviral activity of acyclovir-5'-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug.
2000 Apr 3
The cyclohexene ring system as a furanose mimic: synthesis and antiviral activity of both enantiomers of cyclohexenylguanine.
2000 Feb 24
Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants.
2000 Jan
Antiviral effect of brassinosteroids against herpes virus and arenaviruses.
2000 Jan
Antiviral activity of ganciclovir elaidic acid ester against herpesviruses.
2000 Mar
Guanosine analogues as anti-herpesvirus agents.
2000 Oct-Dec
Flow cytometric evaluation of antiviral agents against human herpesvirus 6.
2001
Cough syncope with herpetic tracheobronchitis.
2001 Apr
Treatment of EBV driven lymphoproliferation with erythrophagocytosis: 12 year follow up.
2001 Apr
Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial.
2001 Apr
[Peptide transporter family].
2001 Apr
Acyclovir treatment in 2 patients with benign trigeminal sensory neuropathy.
2001 Apr
Practice parameter: Steroids, acyclovir, and surgery for Bell's palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
2001 Apr 10
Hydrophilic interaction chromatography using amino and silica columns for the determination of polar pharmaceuticals and impurities.
2001 Apr 13
Postherpetic neuralgia. Treatment with amitriptyline is cheaper than with aciclovir.
2001 Apr 7
Painful skin erosions and fever in an infant. Eczema herpeticum.
2001 Feb
Genetic risks of antiviral nucleoside analogues--a survey.
2001 Feb
Viral etiologies of encephalitis in Thai children.
2001 Feb
Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir?
2001 Feb-Mar
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients.
2001 Feb-Mar
Recurrent herpes labialis: efficacy of topical therapy with penciclovir compared with acyclovir (aciclovir).
2001 Jan
Topical treatment of recurrent herpes labialis.
2001 Jan
Aerobic bacterial and fungal infections in peripheral blood stem cell transplants.
2001 Jan
Aseptic meningitis related to valacyclovir.
2001 Jan
Herpetic folliculitis and syringitis simulating acne excoriée.
2001 Jan
Successful outcome with a "quintuple approach" of posttransplant lymphoproliferative disorder.
2001 Jan 15
Progressive outer retinal necrosis in a patient with nephrotic syndrome.
2001 Jan-Feb
Selection and characterization of varicella-zoster virus variants resistant to (R)-9-[4-hydroxy-2-(hydroxymethy)butyl]guanine.
2001 Jun
Mild herpes simplex encephalitis worsening despite acyclovir treatment.
2001 Mar
Long-term high-dose acyclovir and AIDS-related non-Hodgkins lymphoma.
2001 Mar 15
The management of varicella-zoster virus exposure and infection in pregnancy and the newborn period. Australasian Subgroup in Paediatric Infectious Diseases of the Australasian Society for Infectious Diseases.
2001 Mar 19
Neurotoxicity of valacyclovir in peritoneal dialysis: a pharmacokinetic study.
2001 Mar-Apr
Coexpression of guanylate kinase with thymidine kinase enhances prodrug cell killing in vitro and suppresses vascular smooth muscle cell proliferation in vivo.
2001 May
Oral recurrent human herpes virus infection and bone marrow transplantation survival.
2001 May
Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir.
2001 May
Enhancement of the anti-herpetic effect of trichosanthin by acyclovir and interferon.
2001 May 11
Synthesis and biological evaluation of purine-containing butenolides.
2001 May 24
Patents

Sample Use Guides

Acute Treatment of Herpes Zoster: 800 mg every 4 hours orally, 5 times daily for 7 to 10 days. Genital Herpes: Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.
Route of Administration: Other
In Vitro Use Guide
Penciclovir (PCV) and acyclovir are acyclic guanine analogs which inhibit herpes simplex virus (HSV) DNA polymerase. Their 50% infective doses were 0.5 to 0.8 microgram/ml for clinical isolates of HSV-1 and 1.3 to 2.2 micrograms/ml for HSV-2.
Substance Class Chemical
Created
by admin
on Sat Jun 26 12:07:49 UTC 2021
Edited
by admin
on Sat Jun 26 12:07:49 UTC 2021
Record UNII
MZ1IW7Q79D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VALACYCLOVIR
MI   VANDF  
Common Name English
VALACICLOVIR [WHO-DD]
Common Name English
L-VALINE 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER
Systematic Name English
VALACICLOVIR
INN   WHO-DD  
INN  
Official Name English
VALACYCLOVIR [MI]
Common Name English
VALACV
Common Name English
VALACICLOVIR [INN]
Common Name English
L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER
Common Name English
L-VALINE, ESTER WITH 9-((2-HYDROXYETHOXY)METHYL)GUANINE
Common Name English
VALACYCLOVIR [VANDF]
Common Name English
L-VALINE ESTER WITH 9-((2-HYDROXYETHOXY)METHYL)GUANINE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C281
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000175459
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000180187
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
WHO-ATC J05AB11
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NCI_THESAURUS C29575
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NCI_THESAURUS C1556
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000175459
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
LIVERTOX 1014
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
WHO-VATC QJ05AB11
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000020060
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000175459
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000175468
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
NDF-RT N0000180188
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
Code System Code Type Description
EVMPD
SUB00003MIG
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
RXCUI
73645
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL1349
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
MESH
C084555
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
CAS
124832-26-4
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
HSDB
8084
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
INN
7106
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
EPA CompTox
124832-26-4
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
WIKIPEDIA
VALACICLOVIR
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
PUBCHEM
135398742
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
MERCK INDEX
M11355
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
2798
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
DRUG BANK
DB00577
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
FDA UNII
MZ1IW7Q79D
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
LACTMED
Valacyclovir
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
NCI_THESAURUS
C28235
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
IUPHAR
4824
Created by admin on Sat Jun 26 12:07:49 UTC 2021 , Edited by admin on Sat Jun 26 12:07:49 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC