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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H20N6O4.ClH.H2O
Molecular Weight 378.812
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VALACYCLOVIR HYDROCHLORIDE MONOHYDRATE

SMILES

O.Cl.CC(C)[C@H](N)C(=O)OCCOCN1C=NC2=C1N=C(N)NC2=O

InChI

InChIKey=KNOVZDRKHSHEQN-JZGIKJSDSA-N
InChI=1S/C13H20N6O4.ClH.H2O/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);1H;1H2/t8-;;/m0../s1

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C13H20N6O4
Molecular Weight 324.3357
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://www.ncbi.nlm.nih.gov/pubmed/6313598 | https://www.ncbi.nlm.nih.gov/pubmed/2828440 | https://www.ncbi.nlm.nih.gov/pubmed/202961

Acyclovir is a synthetic antiviral nucleoside analogue. A screening program for antiviral drugs begun at Burroughs Wellcome in the 1960s resulted in the discovery of acyclovir in 1974. Preclinical investigation brought the drug to clinical trials in 1977 and the first form of the drug (topical) was available to physicians in 1982. Activity of acyclovir is greatest against herpes 1 and herpes 2, less against varicella zoster, still less against Epstein-Barr, and very little against cytomegalovirus. Acyclovir is an antiviral agent only after it is phosphorylated in infected cells by a viral-induced thymidine kinase. Acyclovir monophosphate is phosphorylated to diphosphate and triphosphate forms by cellular enzymes in the infected host cell where the drug is concentrated. Acyclovir triphosphate inactivates viral deoxyribonucleic acid polymerase.

CNS Activity

CNS Penetrant
2554
Curator's Comment: Valacyclovir hydrochloride is rapidly converted to acyclovir which was detected in CSF after oral administration of valacyclovir.

Originator

Approval Year

1982
100
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Inhibitor
8297
 0.08 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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

1982
Primary
Approved
8429
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

1982
Primary
Approved
8429
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

2004
Primary
Approved
8429
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

2004
Primary
Approved
8429
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

2004
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
599.2 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17692728
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
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17692728
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
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17692728
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%
EXPERIMENT
https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf
ACYCLOVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OAT1
599

OAT2
145

OAT3
642

OAT4
146

OCT1
512

OCT2
647

OATP1B1
788

OATP1B3
706

OATP2B1
123

CYP1A2
1524
OAT1
326

OAT2
115

OAT3
339

OAT4
78

OCT1
327

OCT2
355

MRP2
205

MATE1
135

MATE2
96

BCRP
561
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OAT2
147
 no
OAT4
146
 no
OATP1B1
803
 no
OATP1B3
715
 no
OATP2B1
126
 no
OCT2
648
 no
CYP1A2
1692
 weak
OAT1
603
 yes
OAT3
644
 yes
OCT1
543
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
OAT2
115
 no
OAT3
339
 no
OAT4
78
 no
OCT2
355
 no
BCRP
561
 yes
MATE1
135
 yes
MATE2
96
 yes
MRP2
205
 yes
OAT1
326
 yes
OCT1
327
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:2453
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2453
ChemicalBook
CB7126677
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7126677
MolPort
MolPort-000-768-994
https://www.molport.com/shop/molecule-link/MolPort-000-768-994
MolPort
MolPort-001-889-834
https://www.molport.com/shop/molecule-link/MolPort-001-889-834
MolPort
MolPort-003-940-063
https://www.molport.com/shop/molecule-link/MolPort-003-940-063
Selleck Chemicals
Acyclovir(Aciclovir)
http://www.selleckchem.com/products/Acyclovir(Aciclovir).html
ZINC
ZINC000001530555
http://zinc15.docking.org/substances/ZINC000001530555
eMolecules
29702921
https://www.emolecules.com/cgi-bin/more?vid=29702921
eMolecules
768732
https://www.emolecules.com/cgi-bin/more?vid=768732
eMolecules
901331
https://www.emolecules.com/cgi-bin/more?vid=901331
PubMed

PubMed

TitleDatePubMed
Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir].
1989 Oct
Flow cytometric evaluation of antiviral agents against human herpesvirus 6.
2001
Atypical Herpes simplex keratitis (HSK) presenting as a perforated corneal ulcer with a large infiltrate in a contact lens wearer: multinucleated giant cells in the Giemsa smear offered a clue to the diagnosis.
2001
A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients.
2001
Prophylaxis against herpesvirus infections in transplant recipients.
2001
Management of neonatal herpes simplex virus infection.
2001
Rotavirus encephalopathy: pathogenesis reviewed.
2001 Apr
Treatment of EBV driven lymphoproliferation with erythrophagocytosis: 12 year follow up.
2001 Apr
[Peptide transporter family].
2001 Apr
Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo.
2001 Apr
Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence mutagenesis improve prodrug-mediated tumor cell killing.
2001 Apr 1
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
[Photoallergy to Zovirax cream].
2001 Feb
Painful skin erosions and fever in an infant. Eczema herpeticum.
2001 Feb
Prophylaxis of intravenous immunoglobulin and acyclovir in perinatal varicella.
2001 Feb
Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.
2001 Feb
Anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)-cycloprop-1'-yl]methyl] x guanine (A-5021) in vitro and in vivo.
2001 Feb
Genetic risks of antiviral nucleoside analogues--a survey.
2001 Feb
Viral etiologies of encephalitis in Thai children.
2001 Feb
Eczema herpeticum in parthenium dermatitis.
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
Antiviral drugs can inhibit lymphocyte apoptosis induced by cytomegalovirus antigens.
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
[Valaciclovir in the treatment of initial infection by genital herpes virus: comparative study].
2001 Jan
Epstein-Barr virus-related lymphoproliferative disease complicating childhood acute lymphoblastic leukemia: no recurrence after unrelated donor bone marrow transplantation.
2001 Jan
Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir.
2001 Jan
Recurrent lumbosacral herpes simplex in the bedridden hospitalized patient.
2001 Jan
Neonatal herpes simplex and incontinentia pigmenti.
2001 Jan-Feb
Crossing diagnostic borders: herpes encephalitis complicated by cultural and language barriers.
2001 Jan-Feb
Selection and characterization of varicella-zoster virus variants resistant to (R)-9-[4-hydroxy-2-(hydroxymethy)butyl]guanine.
2001 Jun
[Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease].
2001 Mar
[Benign acute ataxia in an adult with VZV infection].
2001 Mar
A pilot study of treatment of herpes labialis with 1072 nm narrow waveband light.
2001 Mar
[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?].
2001 Mar
A 35-year-old man with recurrent aseptic meningitis.
2001 Mar
Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease Study Group.
2001 Mar
Investigation of aciclovir-resistant herpes simplex virus I infection in a bone marrow transplantation unit: genotyping shows that different strains are involved.
2001 Mar
Predictive modeling and heterogeneity of baseline risk in meta-analysis of individual patient data.
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
[Intrauterine herpes simplex virus infection].
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
Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study.
2001 May
Synthesis and biological evaluation of purine-containing butenolides.
2001 May 24
FV-100 versus valacyclovir for the prevention of post-herpetic neuralgia and the treatment of acute herpes zoster-associated pain: A randomized-controlled trial.
2017 Jul
Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology.
2017 Mar
Patents

Patents

04146715
11
04199574
9
05565565
9
05567816
8
05583225
8
05688948
8
06107302
8
06262254
8
06887997
8
JP2008510795A
76
JP2009501065A
33
JP2010530906A
11
JP2011528275A
455
JP2012500104A
107
JP2873313B2
8
JP4503896B2
20
JPH04139130A
8
JPH05255329A
8
JPH07258256A
8
JPH09136842A
8
US20070021444
8
WO2016201306
8

Sample Use Guides

In Vivo Use Guide
250 mg three times a day for 14 days
Route of Administration: Oral
In Vitro Use Guide
In uptake studies using valacyclovir, the extraction solution (water/methanol, 50:50) was added to the Caco-2 cells after the uptake period. After standing for 1 h at room temperature, the solutions were centrifuged and the supernatants were filtered. The filtrate was analyzed by highperformance liquid chromatography (HPLC). Valacyclovir showed a marked inhibitory effect (K=440 +/- 29mkM) on [14C]glycylsarcosine uptake via the apical PEPT1.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:16:55 GMT 2023
Edited
by admin
on Sat Dec 16 08:16:55 GMT 2023
Record UNII
JF64RVR4E3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VALACYCLOVIR HYDROCHLORIDE MONOHYDRATE
Common Name English
VALACICLOVIR HYDROCHLORIDE MONOHYDRATE
Common Name English
L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, HYDROCHLORIDE, HYDRATE (1:1:1)
Systematic Name English
VALACICLOVIR HYDROCHLORIDE HYDRATE
Common Name English
Valaciclovir hydrochloride hydrate [WHO-DD]
Common Name English
VALACICLOVIR (AS HYDROCHLORIDE MONOHYDRATE)
Common Name English
VALACICLOVIR HYDROCHLORIDE HYDRATE [JAN]
Common Name English
VALACICLOVIR HYDROCHLORIDE HYDRATE [EP MONOGRAPH]
Common Name English
Code System Code Type Description
CAS
1218948-84-5
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
NON-SPECIFIC STOICHIOMETRY
EVMPD
SUB37499
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
FDA UNII
JF64RVR4E3
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
PUBCHEM
135428922
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
CAS
521915-75-3
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
EVMPD
SUB126884
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
DAILYMED
JF64RVR4E3
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
RXCUI
2604686
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
SMS_ID
100000129151
Created by admin on Sat Dec 16 08:16:56 GMT 2023 , Edited by admin on Sat Dec 16 08:16:56 GMT 2023
PRIMARY
Related Record Type Details
Structure of VALACYCLOVIR HYDROCHLORIDE
ANHYDROUS->SOLVATE
Structure of VALACYCLOVIR
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of N-FORMYL VALACYCLOVIR
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of ACYCLOVIR ALANINATE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of GUANINYL VALACYCLOVIR
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of GUANINE
IMPURITY -> PARENT
sum of impurities A and B: maximum 2.0 per cent
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of ACYCLOVIR L-ISOLEUCINATE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of VALACYCLOVIR, D-
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of N-METHYL VALACYCLOVIR
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of 4-DIMETHYLAMINOPYRIDINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (TLC)
EP
Structure of ACYCLOVIR
IMPURITY -> PARENT
sum of impurities A and B: maximum 2.0 per cent
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of (S)-2-((2-IMINO-6-OXO-2,3-DIHYDRO-1H-PURIN-9(6H)-YL)METHOXY)ETHYL 2-((TERT-BUTOXYCARBONYL)AMINO)-3-METHYLBUTANOATE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (TLC)
EP
Structure of N-ETHYL VALACYCLOVIR
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of BIS VALACYCLOVIR
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of 9-(2-ACETOXYETHOXYMETHYL)GUANINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
Structure of ACYCLOVIR
ACTIVE MOIETY
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