VALACYCLOVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H20N6O4
Molecular Weight	324.3357
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	324.3357
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/3680558 | https://www.ncbi.nlm.nih.gov/pubmed/3790156 | https://www.ncbi.nlm.nih.gov/pubmed/2159990 | Leoung, G.S. (1989) Opportunistic Infections in Patients with the Acquired Immunodeficiency Syndrome, page 207, retrieved from: https://books.google.ru/books?id=As56gGv7E_YChttps://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidine kinase 17 Target ID: CHEMBL1820 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Inhibitor 8504
Human herpesvirus 1 DNA polymerase 24 Target ID: CHEMBL1872 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf	Inhibitor 8504		0.08 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Herpes zoster infections 15 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/18603slr027_zovirax_lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf	Primary	Approved 8583	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
Herpes simplex infection 28 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/18603slr027_zovirax_lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf	Primary	Approved 8583	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
Cold sores 11 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Primary	Approved 8583	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
Genital herpes 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Primary	Approved 8583	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
Herpes zoster infections 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Primary	Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 725 OAT2 153 OAT3 747 OAT4 150 OCT1 620 OCT2 779 OATP1B1 1079 OATP1B3 961 OATP2B1 157 CYP1A2 2153	OAT1 395 OAT2 125 OAT3 391 OAT4 93 OCT1 393 OCT2 434 MRP2 252 MATE1 182 MATE2 98 BCRP 697

Drug as perpetrator

Target	Modality	Activity
OAT2 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT4 150	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OATP2B1 162	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers	weak
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes

Drug as victim

Target	Modality	Activity
OAT2 125	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT3 391	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT4 93	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21859328/	yes
MATE1 182	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MATE2 98	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31341258/	yes
OAT1 395	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/\|https://pubmed.ncbi.nlm.nih.gov/31341258/	yes
OCT1 393	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2453	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2453
ChemicalBook	CB7126677	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7126677
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
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

PubMed

Title	Date	PubMed
Selective activity of various antiviral compounds against HHV-7 infection.	1999 Aug	10480261
Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs.	1999 Dec	10582877
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	10027651
Nucleosides and nucleotides. 185. Synthesis and biological activities of 4'alpha-C-branched-chain sugar pyrimidine nucleosides.	1999 Jul 29	10425099
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
[Cerebral and renal toxicity of acyclovir in a patient treated for meningoencephalitis].	1999 Nov	10615548
Acute renal insufficiency due to oral acyclovir in a man with sickle cell trait.	1999 Nov	10586837
Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicella-zoster virus resistant to acyclovir.	1999 Oct	10508017
Synthesis and antiviral activity of acyclovir-5'-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug.	2000 Apr 3	10762044
Highly potent and selective inhibition of varicella-zoster virus by bicyclic furopyrimidine nucleosides bearing an aryl side chain.	2000 Dec 28	11150169
The cyclohexene ring system as a furanose mimic: synthesis and antiviral activity of both enantiomers of cyclohexenylguanine.	2000 Feb 24	10691698
Antiviral activity of ganciclovir elaidic acid ester against herpesviruses.	2000 Mar	10771080
Metabolism and mode of inhibition of varicella-zoster virus by L-beta-5-bromovinyl-(2-hydroxymethyl)-(1,3-dioxolanyl)uracil is dependent on viral thymidine kinase.	2000 Nov	11040060
Guanosine analogues as anti-herpesvirus agents.	2000 Oct-Dec	11200257
Management of neonatal herpes simplex virus infection.	2001	11269641
Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer.	2001	11250742
Heart transplantation and the Batista operation for children with refractory heart failure.	2001 Apr	11316125
Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial.	2001 Apr	11298543
Acyclovir treatment in 2 patients with benign trigeminal sensory neuropathy.	2001 Apr	11289180
Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo.	2001 Apr	11259565
Postherpetic neuralgia. Pathogenesis of postherpetic neuralgia should be determined.	2001 Apr 7	11290628
Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.	2001 Feb	11260488
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	11248363
Eczema herpeticum in parthenium dermatitis.	2001 Feb	11205385
Antiviral drugs can inhibit lymphocyte apoptosis induced by cytomegalovirus antigens.	2001 Feb-Mar	11267517
[Valaciclovir in the treatment of initial infection by genital herpes virus: comparative study].	2001 Jan	11256241
Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir.	2001 Jan	11219491
Recurrent lumbosacral herpes simplex in the bedridden hospitalized patient.	2001 Jan	11204597
Herpetic folliculitis and syringitis simulating acne excoriée.	2001 Jan	11176676
Neonatal herpes simplex and incontinentia pigmenti.	2001 Jan-Feb	11207986
[Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease].	2001 Mar	11322055
Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease Study Group.	2001 Mar	11248812
Predictive modeling and heterogeneity of baseline risk in meta-analysis of individual patient data.	2001 Mar	11223322
[Intrauterine herpes simplex virus infection].	2001 Mar-Apr	11305194
Oral recurrent human herpes virus infection and bone marrow transplantation survival.	2001 May	11346734
Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.	2001 May	11311761
Contact dermatitis from topical antiviral drugs.	2001 May	11298689

Patents

Sample Use Guides

In Vivo Use Guide

Valacyclovir may be given without regard to meals. Cold Sores (Herpes Labialis): The recommended dosage of Valacyclovir for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore. Genital Herpes: Initial Episode: The recommended dosage of Valacyclovir for treatment of initial genital herpes is 1 gram twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms. Recurrent Episodes: The recommended dosage of Valacyclovir for treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode.

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 `Wed Apr 02 08:20:13 GMT 2025` Edited by `admin` on `Wed Apr 02 08:20:13 GMT 2025`
Record UNII	MZ1IW7Q79D
Record Status	`Validated (UNII)`
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Name

Type

Language

VALACYCLOVIR

Common Name

English

VALACICLOVIR

Preferred 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

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