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References

Trials

Economics

Properties

Spectra

Taxonomy

Acyclovir

Targets (3)Transporters (6)Biointeractions (11)

Identification

Name

Acyclovir

Accession Number

DB00787 (APRD00567, EXPT00406, DB05347)

Type

Small Molecule

Groups

Approved

Description

A guanosine analog antiviral drug that acts as an antimetabolite. Aciclovir is used for the treatment of herpes simplex virus infections, varicella zoster (chickenpox) and herpes zoster (shingles).

Aciclovir has also been investigated for the treatment of herpes labialis applied using an iontophoretic device. Currently approved drugs for the treatment of herpes labialis (cold sores) exhibit low levels of efficacy due to the limited ability of the drugs to penetrate the skin to the site where the herpes virus is replicating. Iontophoresis uses electric current to enhance the delivery of drugs through the skin.

Synonyms

Aciclovir
Aciclovirum
Acycloguanosine

External IDs

NSC-645011

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Acyclovir sodium	927L42J563	69657-51-8	RMLUKZWYIKEASN-UHFFFAOYSA-M

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Acyclovir	Tablet	400 mg	Oral	Sanis Health Inc	2010-04-05	Not applicable
Acyclovir	Tablet	800 mg	Oral	Sanis Health Inc	2010-04-05	2014-08-01
Acyclovir	Tablet	200 mg	Oral	Sanis Health Inc	2010-04-05	2014-08-01
Acyclovir Sodium for Injection	Powder, for solution	1 g	Intravenous	Abbott	1998-02-11	2007-07-31
Acyclovir Sodium for Injection	Powder, for solution	500 mg	Intravenous	Abbott	1998-02-11	2007-07-31
Acyclovir Sodium for Injection	Powder, for solution	1 g	Intravenous	Novopharm Limited	1998-02-04	2005-08-10
Acyclovir Sodium for Injection	Powder, for solution	500 mg	Intravenous	Novopharm Limited	1998-02-04	Not applicable
Acyclovir Sodium Injection	Solution	25 mg	Intravenous	Ivax Pharmaceuticals Incorporated	Not applicable	Not applicable
Acyclovir Sodium Injection	Solution	50 mg	Intravenous	Fresenius Kabi	1998-05-08	Not applicable
Acyclovir Sodium Injection	Solution	25 mg	Intravenous	Pfizer	1998-03-18	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Acyclovir	Tablet	800 mg/1	Oral	Golden State Medical Supply	2013-05-31	Not applicable
Acyclovir	Tablet	800 mg/1	Oral	A-S Medication Solutions	2013-11-29	Not applicable
Acyclovir	Suspension	200 mg/5mL	Oral	Preferreed Pharmaceuticals Inc.	2011-03-18	Not applicable
Acyclovir	Tablet	400 mg/1	Oral	A-S Medication Solutions	2009-10-22	Not applicable
Acyclovir	Capsule	200 mg/1	Oral	Pd Rx Pharmaceuticals, Inc.	2006-03-20	Not applicable
Acyclovir	Capsule	200 mg/1	Oral	Cadila Pharmaceuticals Limited	2014-03-11	2014-03-11
Acyclovir	Capsule	200 mg/1	Oral	Av Pak	2013-05-02	Not applicable
Acyclovir	Tablet	400 mg/1	Oral	Cardinal Health	1999-03-05	Not applicable
Acyclovir	Tablet	800 mg/1	Oral	Remedy Repack	2011-05-09	2011-05-10
Acyclovir	Capsule	200 mg/1	Oral	bryant ranch prepack	2015-02-01	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Xerese	Acyclovir (5 %) + Hydrocortisone (1 %)	Cream	Topical	Valeant Canada Lp Valeant Canada S.E.C.	2013-07-26	Not applicable
Xerese	Acyclovir (50 mg/1g) + Hydrocortisone (10 mg/1g)	Cream	Topical	Valeant Pharmaceuticals North America	2009-07-31	Not applicable
Xerese	Acyclovir (50 mg/1g) + Hydrocortisone (10 mg/1g)	Cream	Topical	Meda Pharmaceuticals Ltd	2010-07-15	2013-02-28

International/Other Brands

Zovir

Categories

UNII

X4HES1O11F

CAS number

59277-89-3

Weight

Not Available

Chemical Formula

C₈H₁₁N₅O₃

InChI Key

MKUXAQIIEYXACX-UHFFFAOYSA-N

InChI

Not Available

IUPAC Name

Not Available

SMILES

Not Available

Pharmacology

Indication

For the treatment and management of herpes zoster (shingles), genital herpes, and chickenpox.

Associated Conditions

Pharmacodynamics

Aciclovir (INN) or acyclovir (USAN, former BAN) is a synthetic deoxyguanosine analog and it is the prototype antiviral agent that is activated by viral thymidine kinase. The selective activity of aciclovir is due to its affinity for the thymidine kinase enzyme encoded by HSV and VZV. EC50 value of acyclovir against clinical herpes virus isolates was 1.3 μM (range: < 0.56 to 3.3 μM).

Mechanism of action

Viral (HSV-1, HSV-2 and VZV) thymidine kinase converts aciclovir to the aciclovir monophosphate, which is then converted to the diphosphate by cellular guanylate kinase, and finally to the triphosphate by phosphoglycerate kinase, phosphoenolpyruvate carboxykinase, and pyruvate kinase. Aciclovir triphosphate competitively inhibits viral DNA polymerase and competes with the natural deoxyguanosine triphosphate, for incorporation into viral DNA. Once incorporated, aciclovir triphosphate inhibits DNA synthesis by acting as a chain terminator. One may consider aciclovir to be a prodrug as it is metabolized to more active compounds. Aciclovir is selective and low in cytotoxicity as the cellular thymidine kinase of normal, uninfected cells does not use aciclovir effectively as a substrate.

Target	Actions	Organism
AThymidine kinase	potentiator	HHV-1
ADNA polymerase catalytic subunit	inhibitor	HHV-1
ADNA polymerase catalytic subunit	inhibitor	HHV-3

Absorption

The oral bioavailability is 10% to 20%, and decreases with increasing dose. Food does not affect the absorption of acyclovir. The following are the pharmacokinetic parameters for 50 mg buccal tablet, Sitavig, in the saliva: AUC 0 - 24 hours = 2900±2400 mcg.h/mL; Cmax = 440±241 mcg/mL; Tmax = 7.95 ± 4.08 hours.

Volume of distribution

Not Available

Protein binding

9%-33%

Metabolism

Hepatic, Acyclovir is metabolized to 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8 hydroxy-acyclovir (8-OH-ACV) by oxidation and hydroxylation. It is suggested in studies that acyclovir is first metabolized to acyclovir aldehyde by alcohol dehydrogenase and then converted to CMMG. The build up of acyclovir aldehyde may be the cause of acyclovir-induced nephrotoxicity in the absence of crystalluria.

Acyclovir
9-carboxymethoxymethylguanine

Route of elimination

Primarily excreted unchanged by the kidneys via active tubular secretion.

Half life

2.5-3.3 hours

Clearance

Not Available

Toxicity

Aciclovir may cause nephrotoxicity (crystallization of aciclovir within renal tubules, elevation of serum creatinine, transient), and neurotoxicity (coma, hallucinations, lethargy, seizures, tremors). Nephrotoxicity and neurotoxicity usually resolve after cessation of aciclovir therapy. However, there is no well-defined relationship between aciclovir concentrations in the blood and these adverse effects.

Affected organisms

Human Herpes Virus

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
3-isobutyl-1-methyl-7H-xanthine	The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Acyclovir.
6-O-benzylguanine	The serum concentration of 6-O-benzylguanine can be increased when it is combined with Acyclovir.
7-Deazaguanine	The serum concentration of 7-Deazaguanine can be increased when it is combined with Acyclovir.
7,9-Dimethylguanine	The serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Acyclovir.
8-azaguanine	The serum concentration of 8-azaguanine can be increased when it is combined with Acyclovir.
8-chlorotheophylline	The serum concentration of 8-chlorotheophylline can be increased when it is combined with Acyclovir.
9-Deazaguanine	The serum concentration of 9-Deazaguanine can be increased when it is combined with Acyclovir.
9-Methylguanine	The serum concentration of 9-Methylguanine can be increased when it is combined with Acyclovir.
Abacavir	Acyclovir may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abiraterone	The serum concentration of Acyclovir can be increased when it is combined with Abiraterone.

Food Interactions

Increase liquid intake.
Take without regard to meals.

References

Synthesis Reference

US4294831

General References

O'Brien JJ, Campoli-Richards DM: Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989 Mar;37(3):233-309. [PubMed:2653790]
Gunness P, Aleksa K, Bend J, Koren G: Acyclovir-induced nephrotoxicity: the role of the acyclovir aldehyde metabolite. Transl Res. 2011 Nov;158(5):290-301. doi: 10.1016/j.trsl.2011.07.002. Epub 2011 Aug 3. [PubMed:22005269]
Morrel EM, Spruance SL, Goldberg DI: Topical iontophoretic administration of acyclovir for the episodic treatment of herpes labialis: a randomized, double-blind, placebo-controlled, clinic-initiated trial. Clin Infect Dis. 2006 Aug 15;43(4):460-7. Epub 2006 Jul 3. [PubMed:16838235]

External Links

Human Metabolome Database: HMDB0014925
KEGG Drug: D00222
KEGG Compound: C06810
PubChem Compound: 2022
PubChem Substance: 46506002
ChemSpider: 1945
BindingDB: 50021776
ChEBI: 2453
ChEMBL: CHEMBL184
Therapeutic Targets Database: DNC000157
PharmGKB: PA448045
HET: AC2
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Aciclovir

ATC Codes

S01AD03 — Aciclovir

J05AB01 — Aciclovir

D06BB53 — Aciclovir, combinations

D06BB03 — Aciclovir

AHFS Codes

84:04.06 — Antivirals
08:18.32 — Nucleosides and Nucleotides

PDB Entries

1pwy / 2ki5 / 3mjr / 4da7 / 5i3c

MSDS

Download (37 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Active Not Recruiting	Treatment	Progressive Multiple Sclerosis	1
1	Completed	Not Available	Infection NOS	1
1	Completed	Treatment	Acute and Chronic Inflammation / Autoimmune Diseases / Disorder of Pleura and Pleural Cavity / Disorder of Synovium / Felty's Syndrome / Rheumatoid Arthritis / Rheumatoid Nodules / Sjögren's Syndrome	1
1	Completed	Treatment	Herpes Simplex Virus / Neonatal Sepsis	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
1	Completed	Treatment	Progressive Multiple Sclerosis	2
1, 2	Completed	Treatment	Acute Undifferentiated Leukemia (AUL) / B-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / L1 Adult Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Adult Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia / Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia / T-cell Adult Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia	1
1, 2	Completed	Treatment	Herpes Simplex	1
1, 2	Completed	Treatment	Kidney Diseases / Transplantation, Kidney	1
2	Active Not Recruiting	Treatment	Herpes Labialis	1
2	Active Not Recruiting	Treatment	Lung Cancer Non-Small Cell Cancer (NSCLC)	1
2	Completed	Prevention	Critical Illness	1
2	Completed	Prevention	Herpes simplex of the genitals / Ulcers	1
2	Completed	Treatment	Chickenpox / Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Herpes Labialis	1
2	Completed	Treatment	Herpes simplex of the genitals / Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Herpesvirus 2, Human / Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Metastatic Castration Resistant Prostate Cancer	1
2	Recruiting	Supportive Care	Stem Cell Transplant Complications	1
2, 3	Completed	Prevention	HIV-1 and HSV-2 Coinfection / Human Immunodeficiency Virus (HIV) Infections	1
2, 3	Completed	Treatment	Herpes Simplex / Human Immunodeficiency Virus (HIV) Infections / Ulcers	1
2, 3	Unknown Status	Treatment	Menière's Disease	1
2, 3	Withdrawn	Treatment	Herpes Simplex	1
3	Active Not Recruiting	Treatment	Drug Use for Unapproved Schedule	1
3	Completed	Not Available	VZV Infection After Bone Marrow Transplantation	1
3	Completed	Prevention	Cytomegalovirus / Transplantation, Bone Marrow	1
3	Completed	Prevention	Herpes simplex of the genitals / HIV Seronegativity / Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Prevention	Herpes Simplex, Genital / Human Immunodeficiency Virus (HIV) Infections / Sexually Transmitted Disease (STD)	1
3	Completed	Supportive Care	Cancers	1
3	Completed	Supportive Care	Herpes Simplex	1
3	Completed	Treatment	Chickenpox / Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Treatment	Genital Herpes	1
3	Completed	Treatment	Herpes Labialis	3
3	Completed	Treatment	Herpes Simplex	4
3	Completed	Treatment	Herpes Simplex / Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Treatment	Herpes Simplex / Keratitis, Herpetic / Ocular Herpes Simplex	1
3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Infections, Cytomegalovirus	1
3	Recruiting	Prevention	CMV Disease	1
3	Recruiting	Treatment	Disseminated Sclerosis	1
3	Recruiting	Treatment	Herpes Zoster	1
3	Unknown Status	Treatment	Herpes Simplex	1
3	Unknown Status	Treatment	Keratitis, Herpetic / Ocular Herpes Simplex	1
4	Active Not Recruiting	Not Available	Genital Herpes	1
4	Completed	Prevention	Herpes / Human Immunodeficiency Virus (HIV)	1
4	Completed	Treatment	Genital Herpes	2
4	Completed	Treatment	Genital Herpes / Human Immunodeficiency Virus (HIV) Infections	1
4	Completed	Treatment	Healthy Volunteers	1
4	Completed	Treatment	Herpes Simplex Infection / Human Immunodeficiency Virus (HIV) Infections	1
4	Completed	Treatment	Relapsing Remitting Multiple Sclerosis (RRMS)	1
4	Recruiting	Treatment	Viral Pneumonia	1
4	Unknown Status	Treatment	Herpes Zoster	1
4	Unknown Status	Treatment	Reccurent Herpes Labialis	1
Not Available	Completed	Not Available	Genital Herpes	1
Not Available	Completed	Basic Science	Dermatologic Disorders	1
Not Available	Completed	Treatment	Cytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections	1
Not Available	Completed	Treatment	Facial Paralysis	1
Not Available	Completed	Treatment	Genital Herpes	1
Not Available	Completed	Treatment	Herpes Simplex / Human Immunodeficiency Virus (HIV) Infections	4
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Oral hairy leukoplakia	1
Not Available	Completed	Treatment	Ulcers of Female Genital Organs	1
Not Available	Recruiting	Not Available	Children; Infection / Newborn; Infection	1
Not Available	Recruiting	Not Available	Meningitis, Aseptic	1
Not Available	Recruiting	Treatment	Uveitis	1

Pharmacoeconomics

Manufacturers

Actavis elizabeth llc
Apotex inc etobicoke site
Belcher pharmaceuticals inc
Dava pharmaceuticals inc
Genpharm inc
Ivax pharmaceuticals inc sub teva pharmaceuticals usa
Lek pharmaceutical and chemical co dd
Mylan pharmaceuticals inc
Ranbaxy laboratories ltd
Roxane laboratories inc
Stason industrial corp
Teva pharmaceuticals usa inc
Teva pharmaceuticals usa
Watson laboratories inc
Glaxosmithkline
Actavis mid atlantic llc
Hi tech pharmacal co inc
Carlsbad technology inc
Mylan laboratories inc
Abbott laboratories
Baxter healthcare corp anesthesia and critical care
Apothecon inc div bristol myers squibb
App pharmaceuticals llc
Bedford laboratories div ben venue laboratories inc
Hospira inc
Teva parenteral medicines inc

Packagers

Actavis Group
Advanced Pharmaceutical Services Inc.
Amerisource Health Services Corp.
Amneal Pharmaceuticals
Apotex Inc.
Apotheca Inc.
Apothecary Shop Wholesale
APP Pharmaceuticals
AQ Pharmaceuticals Inc.
A-S Medication Solutions LLC
Atlantic Biologicals Corporation
Bedford Labs
Ben Venue Laboratories Inc.
Bryant Ranch Prepack
BTA Pharmaceuticals
Cardinal Health
Carlsbad Technology Inc.
Comprehensive Consultant Services Inc.
Corepharma LLC
DAVA Pharmaceuticals
Direct Dispensing Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
DSM Corp.
East Coast Medical Network Inc.
Eczacibasi Health Products Co.
GlaxoSmithKline Inc.
Goldline Laboratories Inc.
H.J. Harkins Co. Inc.
Heritage Pharmaceuticals
Hi Tech Pharmacal Co. Inc.
Hospira Inc.
Ivax Pharmaceuticals
Kaiser Foundation Hospital
Lake Erie Medical and Surgical Supply
Liberty Pharmaceuticals
Major Pharmaceuticals
Mckesson Corp.
Medvantx Inc.
Meridian Medical Technologies Inc.
Murfreesboro Pharmaceutical Nursing Supply
Mylan
Neuman Distributors Inc.
Novopharm Ltd.
Nucare Pharmaceuticals Inc.
Palmetto Pharmaceuticals Inc.
Patheon Inc.
PCA LLC
PD-Rx Pharmaceuticals Inc.
Pharmaceutical Utilization Management Program VA Inc.
Pharmedix
Pharmpak Inc.
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Ranbaxy Laboratories
Rebel Distributors Corp.
Redpharm Drug
Remedy Repack
Resource Optimization and Innovation LLC
Roxane Labs
Southwood Pharmaceuticals
St Mary's Medical Park Pharmacy
Stason Pharmaceuticals Inc.
Teva Pharmaceutical Industries Ltd.
UDL Laboratories
Watson Pharmaceuticals
Xactdose Inc.
Yung Shin Pharmaceutical Industry Ltd.

Dosage forms

Form	Route	Strength
Capsule	Oral	200 mg/1
Capsule	Oral	400 mg/1
Injection, powder, lyophilized, for solution	Intravenous	1 g/1
Injection, powder, lyophilized, for solution	Intravenous	1000 mg/1
Injection, powder, lyophilized, for solution	Intravenous	1000 mg/20mL
Injection, powder, lyophilized, for solution	Intravenous	500 mg/10mL
Injection, powder, lyophilized, for solution	Intravenous	500 mg/1
Injection, solution	Intravenous	25 mg/1mL
Injection, solution	Intravenous	50 mg/1mL
Ointment	Cutaneous	50 mg/1g
Suspension	Oral	200 mg/5mL
Tablet	Oral	200 mg/1
Tablet	Oral	400 mg/1
Tablet	Oral	400.00 mg/1
Tablet	Oral	800 mg/1
Tablet	Oral	800.00 mg/1
Injection, solution	Intravenous	1000 mg/20mL
Injection, solution	Intravenous	500 mg/10mL
Powder, for solution	Intravenous	500 mg
Solution	Intravenous	25 mg
Solution	Intravenous	50 mg
Tablet	Oral	800 mg
Tablet	Oral	200 mg
Tablet	Oral	400 mg
Tablet	Buccal	50 mg
Tablet, delayed release	Buccal	50 mg/1
Cream	Topical
Cream	Topical	5 %
Cream	Topical	50 mg/1g
Injection, powder, lyophilized, for solution	Intravenous	50 mg/1mL
Ointment	Topical	5 %
Ointment	Topical	50 mg/1g
Powder, for solution	Intravenous	1 g
Suspension	Oral	200 mg
Capsule	Oral	200 mg

Prices

Unit description	Cost	Unit
Zovirax 200 mg/5ml Suspension 473ml Bottle	264.95USD	bottle
Zovirax 5% Ointment 15 gm Tube	191.56USD	tube
Zovirax 5% Cream 5 gm Tube	165.07USD	tube
Zovirax 5% Cream 2 gm Tube	69.44USD	tube
Zovirax 5% cream	30.22USD	g
Zovirax 800 mg tablet	11.83USD	tablet
Zovirax 400 mg tablet	6.09USD	tablet
Zovirax 800 mg Tablet	5.71USD	tablet
Acyclovir 800 mg tablet	3.81USD	tablet
Zovirax 200 mg capsule	3.08USD	capsule
Acyclovir 800 mg Tablet	2.99USD	tablet
Apo-Acyclovir 800 mg Tablet	2.99USD	tablet
Mylan-Acyclovir 800 mg Tablet	2.99USD	tablet
Novo-Acyclovir 800 mg Tablet	2.99USD	tablet
Nu-Acyclovir 800 mg Tablet	2.99USD	tablet
Ratio-Acyclovir 800 mg Tablet	2.99USD	tablet
Zovirax 400 mg Tablet	2.9USD	tablet
Acyclovir 400 mg tablet	2.26USD	tablet
Acyclovir 400 mg Tablet	1.63USD	tablet
Apo-Acyclovir 400 mg Tablet	1.63USD	tablet
Mylan-Acyclovir 400 mg Tablet	1.63USD	tablet
Novo-Acyclovir 400 mg Tablet	1.63USD	tablet
Nu-Acyclovir 400 mg Tablet	1.63USD	tablet
Ratio-Acyclovir 400 mg Tablet	1.63USD	tablet
Zovirax 200 mg Tablet	1.44USD	tablet
Acyclovir 200 mg capsule	1.01USD	capsule
Acyclovir 200 mg Tablet	0.81USD	tablet
Apo-Acyclovir 200 mg Tablet	0.81USD	tablet
Mylan-Acyclovir 200 mg Tablet	0.81USD	tablet
Novo-Acyclovir 200 mg Tablet	0.81USD	tablet
Ratio-Acyclovir 200 mg Tablet	0.81USD	tablet
Acyclovir 200 mg/5ml Suspension	0.3USD	ml
Zovirax 40 mg/ml Suspension	0.28USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2098108	No	2001-07-03	2012-01-29
USRE39264	No	1996-08-02	2016-08-02
US6514980	No	1999-01-24	2019-01-24
US7223387	No	2001-07-24	2021-07-24
US8747896	No	2007-06-03	2027-06-03
US8791127	No	2007-03-23	2027-03-23
US8592434	No	2010-06-16	2030-06-16

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	255 °C	PhysProp
water solubility	2.5 mg/mL at 37°C	FDA label
logP	-1.56	KRISTL,A ET AL. (1993)
Caco2 permeability	-6.15	ADME Research, USCD
pKa	2.27 and 9.25	FDA label

Predicted Properties

Not Available

Predicted ADMET features

Not Available

Spectra

Mass Spec (NIST): Not Available
Spectra: Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as hypoxanthines. These are compounds containing the purine derivative 1H-purin-6(9H)-one. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
Kingdom: Organic compounds
Super Class: Organoheterocyclic compounds
Class: Imidazopyrimidines
Sub Class: Purines and purine derivatives
Direct Parent: Hypoxanthines
Alternative Parents: 6-oxopurines / Pyrimidones / Aminopyrimidines and derivatives / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Primary alcohols / Organopnictogen compounds
show 2 more
Substituents: 6-oxopurine / Hypoxanthine / Aminopyrimidine / Pyrimidone / N-substituted imidazole / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
show 13 more
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: oxopurine, 2-aminopurines (CHEBI:2453)

Targets

Details1. Thymidine kinase

Kind: Protein
Organism: HHV-1
Pharmacological action: Yes
Actions: Potentiator

General Function: Thymidine kinase activity
Specific Function: In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate the...
Gene Name: TK
Uniprot ID: P03176
Uniprot Name: Thymidine kinase
Molecular Weight: 40971.555 Da

References

Bennett MS, Wien F, Champness JN, Batuwangala T, Rutherford T, Summers WC, Sun H, Wright G, Sanderson MR: Structure to 1.9 A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir. FEBS Lett. 1999 Jan 25;443(2):121-5. [PubMed:9989588]

Details2. DNA polymerase catalytic subunit

Kind: Protein
Organism: HHV-1
Pharmacological action: Yes
Actions: Inhibitor

General Function: Rna-dna hybrid ribonuclease activity
Specific Function: Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name: Not Available
Uniprot ID: P04293
Uniprot Name: DNA polymerase catalytic subunit
Molecular Weight: 136419.66 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Sergerie Y, Boivin G: Hydroxyurea enhances the activity of acyclovir and cidofovir against herpes simplex virus type 1 resistant strains harboring mutations in the thymidine kinase and/or the DNA polymerase genes. Antiviral Res. 2008 Jan;77(1):77-80. Epub 2007 Sep 17. [PubMed:17913252]
Suzuki M, Okuda T, Shiraki K: Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2006 Nov;72(2):157-61. Epub 2006 May 30. [PubMed:16797734]
Liu S, Knafels JD, Chang JS, Waszak GA, Baldwin ET, Deibel MR Jr, Thomsen DR, Homa FL, Wells PA, Tory MC, Poorman RA, Gao H, Qiu X, Seddon AP: Crystal structure of the herpes simplex virus 1 DNA polymerase. J Biol Chem. 2006 Jun 30;281(26):18193-200. Epub 2006 Apr 24. [PubMed:16638752]

Details3. DNA polymerase catalytic subunit

Kind: Protein
Organism: HHV-3
Pharmacological action: Yes
Actions: Inhibitor

General Function: Rna-dna hybrid ribonuclease activity
Specific Function: Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name: Not Available
Uniprot ID: P09252
Uniprot Name: DNA polymerase catalytic subunit
Molecular Weight: 134046.615 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Sergerie Y, Boivin G: Hydroxyurea enhances the activity of acyclovir and cidofovir against herpes simplex virus type 1 resistant strains harboring mutations in the thymidine kinase and/or the DNA polymerase genes. Antiviral Res. 2008 Jan;77(1):77-80. Epub 2007 Sep 17. [PubMed:17913252]
Suzuki M, Okuda T, Shiraki K: Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2006 Nov;72(2):157-61. Epub 2006 May 30. [PubMed:16797734]
Liu S, Knafels JD, Chang JS, Waszak GA, Baldwin ET, Deibel MR Jr, Thomsen DR, Homa FL, Wells PA, Tory MC, Poorman RA, Gao H, Qiu X, Seddon AP: Crystal structure of the herpes simplex virus 1 DNA polymerase. J Biol Chem. 2006 Jun 30;281(26):18193-200. Epub 2006 Apr 24. [PubMed:16638752]

Transporters

Details1. Solute carrier family 22 member 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Secondary active organic cation transmembrane transporter activity
Specific Function: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

References

Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798]

Details2. Solute carrier family 22 member 6

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name: SLC22A6
Uniprot ID: Q4U2R8
Uniprot Name: Solute carrier family 22 member 6
Molecular Weight: 61815.78 Da

References

Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798]
Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. [PubMed:10945832]

Details3. Solute carrier family 22 member 8

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name: SLC22A8
Uniprot ID: Q8TCC7
Uniprot Name: Solute carrier family 22 member 8
Molecular Weight: 59855.585 Da

References

Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798]
Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T: Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem. 2002 Oct;83(1):57-66. [PubMed:12358729]
Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713]

Details4. Ileal sodium/bile acid cotransporter

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Bile acid:sodium symporter activity
Specific Function: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
Gene Name: SLC10A2
Uniprot ID: Q12908
Uniprot Name: Ileal sodium/bile acid cotransporter
Molecular Weight: 37713.405 Da

References

Tolle-Sander S, Lentz KA, Maeda DY, Coop A, Polli JE: Increased acyclovir oral bioavailability via a bile acid conjugate. Mol Pharm. 2004 Jan 12;1(1):40-8. [PubMed:15832499]

Details5. Multidrug and toxin extrusion protein 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Monovalent cation:proton antiporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name: SLC47A1
Uniprot ID: Q96FL8
Uniprot Name: Multidrug and toxin extrusion protein 1
Molecular Weight: 61921.585 Da

References

Nies AT, Damme K, Schaeffeler E, Schwab M: Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs. Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1565-77. doi: 10.1517/17425255.2012.722996. Epub 2012 Sep 13. [PubMed:22970772]
Xu Y, Liu X, Wang Y, Zhou N, Peng J, Gong L, Ren J, Luo C, Luo X, Jiang H, Chen K, Zheng M: Combinatorial Pharmacophore Modeling of Multidrug and Toxin Extrusion Transporter 1 Inhibitors: a Theoretical Perspective for Understanding Multiple Inhibitory Mechanisms. Sci Rep. 2015 Sep 2;5:13684. doi: 10.1038/srep13684. [PubMed:26330298]

Details6. Multidrug and toxin extrusion protein 2

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Drug transmembrane transporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name: SLC47A2
Uniprot ID: Q86VL8
Uniprot Name: Multidrug and toxin extrusion protein 2
Molecular Weight: 65083.915 Da

References

Nies AT, Damme K, Schaeffeler E, Schwab M: Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs. Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1565-77. doi: 10.1517/17425255.2012.722996. Epub 2012 Sep 13. [PubMed:22970772]
Yonezawa A, Inui K: Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br J Pharmacol. 2011 Dec;164(7):1817-25. doi: 10.1111/j.1476-5381.2011.01394.x. [PubMed:21457222]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:30