ACYCLOVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H11N5O3
Molecular Weight	225.2046
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(N=CN2COCCO)C(=O)N1

InChI

InChIKey=MKUXAQIIEYXACX-UHFFFAOYSA-N

InChI=1S/C8H11N5O3/c9-8-11-6-5(7(15)12-8)10-3-13(6)4-16-2-1-14/h3,14H,1-2,4H2,(H3,9,11,12,15)

HIDE SMILES / InChI

Molecular Formula	C8H11N5O3
Molecular Weight	225.2046
Charge	0
Count

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidine kinase 16 Target ID: CHEMBL1820 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Inhibitor 8146
Human herpesvirus 1 DNA polymerase 17 Target ID: CHEMBL1872 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf	Inhibitor 8146		0.08 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Herpes zoster infections 14 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 8307	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
Herpes simplex infection 27 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 8307	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
Cold sores 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Primary	Approved 8307	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
Genital herpes 12 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Primary	Approved 8307	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
Herpes zoster infections 14 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020487s016lbl.pdf	Primary	Approved 8307	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

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 584 OAT2 144 OAT3 625 OAT4 145 OCT1 498 OCT2 630 OATP1B1 770 OATP1B3 691 OATP2B1 121 CYP1A2 1463	OAT1 314 OAT2 111 OAT3 328 OAT4 76 OCT1 317 OCT2 336 MRP2 196 MATE1 131 MATE2 93 BCRP 545

Drug as perpetrator

Target	Modality	Activity
OAT2 146	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OATP1B1 785	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OATP1B3 700	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OATP2B1 124	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
CYP1A2 1620	inhibitor 3185 Sources: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers	weak
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
OCT1 513	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes

Drug as victim

Target	Modality	Activity
OAT2 111	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT3 328	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OAT4 76	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
OCT2 336	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	no
BCRP 545	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/21859328/	yes
MATE1 131	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MATE2 93	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MRP2 196	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/31341258/	yes
OAT1 314	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/\|https://pubmed.ncbi.nlm.nih.gov/31341258/	yes
OCT1 317	substrate 3264 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
Flow cytometric evaluation of antiviral agents against human herpesvirus 6.	2001	11345533
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	11325340
A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients.	2001	11291551
Prophylaxis against herpesvirus infections in transplant recipients.	2001	11270937
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
Cough syncope with herpetic tracheobronchitis.	2001 Apr	11344844
Rotavirus encephalopathy: pathogenesis reviewed.	2001 Apr	11328483
Heart transplantation and the Batista operation for children with refractory heart failure.	2001 Apr	11316125
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
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
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
Hydrophilic interaction chromatography using amino and silica columns for the determination of polar pharmaceuticals and impurities.	2001 Apr 13	11355803
Painful skin erosions and fever in an infant. Eczema herpeticum.	2001 Feb	11272689
Prophylaxis of intravenous immunoglobulin and acyclovir in perinatal varicella.	2001 Feb	11271397
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
Genetic risks of antiviral nucleoside analogues--a survey.	2001 Feb	11248359
Viral etiologies of encephalitis in Thai children.	2001 Feb	11224846
Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir?	2001 Feb-Mar	11267547
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients.	2001 Feb-Mar	11267523
Antiviral drugs can inhibit lymphocyte apoptosis induced by cytomegalovirus antigens.	2001 Feb-Mar	11267517
Recurrent herpes labialis: efficacy of topical therapy with penciclovir compared with acyclovir (aciclovir).	2001 Jan	11354919
Topical treatment of recurrent herpes labialis.	2001 Jan	11354913
Aerobic bacterial and fungal infections in peripheral blood stem cell transplants.	2001 Jan	11281391
[Valaciclovir in the treatment of initial infection by genital herpes virus: comparative study].	2001 Jan	11256241
Epstein-Barr virus-related lymphoproliferative disease complicating childhood acute lymphoblastic leukemia: no recurrence after unrelated donor bone marrow transplantation.	2001 Jan	11244444
Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4-triazol.	2001 Jan-Feb	11303556
Selection and characterization of varicella-zoster virus variants resistant to (R)-9-[4-hydroxy-2-(hydroxymethy)butyl]guanine.	2001 Jun	11353604
Mild herpes simplex encephalitis worsening despite acyclovir treatment.	2001 Mar	11355162
[Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease].	2001 Mar	11322055
[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
A 35-year-old man with recurrent aseptic meningitis.	2001 Mar	11263848
Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease Study Group.	2001 Mar	11248812
Investigation of aciclovir-resistant herpes simplex virus I infection in a bone marrow transplantation unit: genotyping shows that different strains are involved.	2001 Mar	11247677
Long-term high-dose acyclovir and AIDS-related non-Hodgkins lymphoma.	2001 Mar 15	11247725
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
[Intrauterine herpes simplex virus infection].	2001 Mar-Apr	11305194
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
Oral recurrent human herpes virus infection and bone marrow transplantation survival.	2001 May	11346734
Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study.	2001 May	11316720
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
Synthesis and biological evaluation of purine-containing butenolides.	2001 May 24	11356110

Patents

Sample Use Guides

In Vivo Use Guide

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 `Fri Dec 16 16:58:42 UTC 2022` Edited by `admin` on `Fri Dec 16 16:58:42 UTC 2022`
Record UNII	X4HES1O11F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ACYCLOVIR

Official Name

English

SITAVIG

Brand Name

English

ZOVIRAX

Brand Name

English

aciclovir [INN]

Common Name

English

ACYCLOVIR [VANDF]

Common Name

English

NSC-758477

Code

English

Aciclovir [WHO-DD]

Common Name

English

ACICLOVIR [JAN]

Common Name

English

ACICLOVIR

Official Name

English

ACYCLOVIR [USP-RS]

Common Name

English

ACICLOVIR [WHO-IP]

Common Name

English

ACICLOVIR [MART.]

Common Name

English

VALACICLOVIR HYDROCHLORIDE HYDRATE IMPURITY B [EP IMPURITY]

Common Name

English

ACYCLOVIR [HSDB]

Common Name

English

VALACICLOVIR HYDROCHLORIDE IMPURITY B [EP IMPURITY]

Common Name

English

GERPEVIR

Common Name

English

NOVIRUS

Common Name

English

9-[(2-Hydroxyethoxy)methyl]guanine

Systematic Name

English

6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-((2-HYDROXYETHOXY)METHYL)-

Systematic Name

English

ACYCLOVIR [MI]

Common Name

English

ACICLOVIR [IARC]

Common Name

English

ACYCLOVIR [ORANGE BOOK]

Common Name

English

NSC-645011

Code

English

AVACLYR

Brand Name

English

ACYCLOVIR [USAN]

Common Name

English

ACICLOVIRUM [WHO-IP]

Common Name

English

ACICLOVIR [EP MONOGRAPH]

Common Name

English

ACYCLOVIR [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C281