VALACYCLOVIR HYDROCHLORIDE DIHYDRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H20N6O4.ClH.2H2O
Molecular Weight	396.827
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of VALACYCLOVIR HYDROCHLORIDE DIHYDRATE

Structure Search

SMILES

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

InChI

InChIKey=QMVFKSCLPIIINF-CZDIJEQGSA-N

InChI=1S/C13H20N6O4.ClH.2H2O/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;2*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	C13H20N6O4
Molecular Weight	324.3357
Charge	0
Count

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

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

Description
Sources: https://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_YChttp://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdfhttps://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 8297
Human herpesvirus 1 DNA polymerase 19 Target ID: CHEMBL1872 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf	Inhibitor 8297		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 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
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 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
Cold sores 11 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	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
Genital herpes 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	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
Herpes zoster infections 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	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

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 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

Target	Modality	Activity
OAT2 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OATP2B1 126	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers	weak
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes

Drug as victim

Target	Modality	Activity
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT4 78	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21859328/	yes
MATE1 135	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MATE2 96	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31341258/	yes
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/\|https://pubmed.ncbi.nlm.nih.gov/31341258/	yes
OCT1 327	substrate 3367 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
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

Title	Date	PubMed
[Cerebral and renal toxicity of acyclovir in a patient treated for meningoencephalitis].	1999 Nov	10615548
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
Acyclovir induced coma in the intensive care unit.	2000 Jun	10853214
Thienothiadiazine 2,2-dioxide acyclonucleosides: synthesis and antiviral activity.	2000 May	10901293
Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.	2000 Oct 15	11023816
Guanosine analogues as anti-herpesvirus agents.	2000 Oct-Dec	11200257
A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients.	2001	11291551
Management of neonatal herpes simplex virus infection.	2001	11269641
Rotavirus encephalopathy: pathogenesis reviewed.	2001 Apr	11328483
Treatment of EBV driven lymphoproliferation with erythrophagocytosis: 12 year follow up.	2001 Apr	11304854
Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial.	2001 Apr	11298543
[Peptide transporter family].	2001 Apr	11296359
Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo.	2001 Apr	11259565
Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence mutagenesis improve prodrug-mediated tumor cell killing.	2001 Apr 1	11306482
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	11294918
Postherpetic neuralgia. Treatment with amitriptyline is cheaper than with aciclovir.	2001 Apr 7	11290647
[Photoallergy to Zovirax cream].	2001 Feb	11275608
Painful skin erosions and fever in an infant. Eczema herpeticum.	2001 Feb	11272689
Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.	2001 Feb	11260488
Viral etiologies of encephalitis in Thai children.	2001 Feb	11224846
Recurrent eczema herpeticum: an underrecognised condition.	2001 Feb	11158702
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients.	2001 Feb-Mar	11267523
Recurrent herpes labialis: efficacy of topical therapy with penciclovir compared with acyclovir (aciclovir).	2001 Jan	11354919
Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir.	2001 Jan	11219491
Reporter genes and imagene.	2001 Jan	11197957
Aseptic meningitis related to valacyclovir.	2001 Jan	11197578
Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.	2001 Jan	11162975
Biliary stricture secondary to donor B-cell lymphoma after orthotopic liver transplantation.	2001 Jan	11150426
Successful outcome with a "quintuple approach" of posttransplant lymphoproliferative disorder.	2001 Jan 15	11211194
Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4-triazol.	2001 Jan-Feb	11303556
Progressive outer retinal necrosis in a patient with nephrotic syndrome.	2001 Jan-Feb	11195746
Mild herpes simplex encephalitis worsening despite acyclovir treatment.	2001 Mar	11355162
[Benign acute ataxia in an adult with VZV infection].	2001 Mar	11319497
A pilot study of treatment of herpes labialis with 1072 nm narrow waveband light.	2001 Mar	11298104
[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?].	2001 Mar	11270274
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
Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.	2001 Mar	11170022
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	11297117
Neurotoxicity of valacyclovir in peritoneal dialysis: a pharmacokinetic study.	2001 Mar-Apr	11359026
Coexpression of guanylate kinase with thymidine kinase enhances prodrug cell killing in vitro and suppresses vascular smooth muscle cell proliferation in vivo.	2001 May	11356082
Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.	2001 May	11311761
Contact dermatitis from topical antiviral drugs.	2001 May	11298689
Enhancement of the anti-herpetic effect of trichosanthin by acyclovir and interferon.	2001 May 11	11356198

Patents

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 `Fri Dec 15 15:47:46 GMT 2023` Edited by `admin` on `Fri Dec 15 15:47:46 GMT 2023`
Record UNII	A7JO128919
Record Status	`Validated (UNII)`
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Name

Type

Language

VALACYCLOVIR HYDROCHLORIDE DIHYDRATE

Common Name

English

L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, MONOHYDROCHLORIDE, DIHYDRATE

Common Name

English

L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, MONOHYDROCHLORIDE DIHYDRATE

Common Name

English

L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, HYDROCHLORIDE, HYDRATE (1:1:2)

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID90198248