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

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
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	2589844
Hepatic and renal effects of azidothymidine and acyclovir on pregnant rats.	2000	11214960
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
Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer.	2001	11250742
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
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
Hydrophilic interaction chromatography using amino and silica columns for the determination of polar pharmaceuticals and impurities.	2001 Apr 13	11355803
Postherpetic neuralgia. Treatment with amitriptyline is cheaper than with aciclovir.	2001 Apr 7	11290647
Postherpetic neuralgia. Pathogenesis of postherpetic neuralgia should be determined.	2001 Apr 7	11290628
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
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
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
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
Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir.	2001 Jan	11219491
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
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
Predictive modeling and heterogeneity of baseline risk in meta-analysis of individual patient data.	2001 Mar	11223322
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
Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.	2001 May	11311761
Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir.	2001 May	11288106
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
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	27943311
Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology.	2017 Mar	28094044

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.

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