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 3.86208006E11
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 3.86208006E11
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 1.07896321E12
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 1.07887683E12
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 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 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
Acute renal insufficiency due to oral acyclovir in a man with sickle cell trait.	1999 Nov	10586837
Interventions for herpes simplex virus epithelial keratitis.	2001	11279774
Management of neonatal herpes simplex virus infection.	2001	11269641
Rotavirus encephalopathy: pathogenesis reviewed.	2001 Apr	11328483
[Peptide transporter family].	2001 Apr	11296359
[Photoallergy to Zovirax cream].	2001 Feb	11275608
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
Persistent verrucous varicella as the initial manifestation of HIV infection.	2001 Feb	11174425
Recurrent eczema herpeticum: an underrecognised condition.	2001 Feb	11158702
Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir?	2001 Feb-Mar	11267547
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
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
Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation.	2001 Jan 15	11170910
[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?].	2001 Mar	11270274
[Intrauterine herpes simplex virus infection].	2001 Mar-Apr	11305194
Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.	2001 May	11311761

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