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targets (3) transporters (4)
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Identification
Name Aciclovir
Accession Number DB00787 (APRD00567, EXPT00406)
Type small molecule
Groups approved
Description

A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
9-Hyroxyethoxymethylguanine
AC2
Aciclovier
Aciclovir Sodium
Acycloguanosine
Acyclovir
Acyclovir Sodium
Wellcome-248u
Salts Not Available
Brand names
Name Company
Alti-Acyclovir
Avirax
Vipral
Virorax
Zovir
Zovirax
Zovirax topical
Brand mixtures
Brand Name Ingredients
Zovirax Injection Zovirax sodium
Categories
  • Antiviral Agents
  • Nucleosides and Nucleotides
CAS number 59277-89-3
Weight Average: 225.2046
Monoisotopic: 225.086189243
Chemical Formula C8H11N5O3
InChI Key InChIKey=MKUXAQIIEYXACX-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
2-amino-9-[(2-hydroxyethoxy)methyl]-6,9-dihydro-3H-purin-6-one
SMILES
NC1=NC(=O)C2=C(N1)N(COCCO)C=N2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Purines and Purine Derivatives
  • Inosines
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
  • Inosines
Pharmacology
Indication For the treatment and management of herpes zoster (shingles), genital herpes, and chickenpox
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.
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.
Absorption Oral: bioavailability 10 to 20%
Volume of distribution Not Available
Protein binding 9%-33%
Metabolism Hepatic, the only major urinary metabolite that has been detected is 9-carboxymethoxymethylguanine.
Route of elimination Acyclovir is cleared renally.
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
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
Dosage forms
Form Route Strength
Cream Topical
Ointment Topical
Powder, for solution Intravenous
Solution Intravenous
Suspension Oral
Tablet Oral
Prices
Unit description Cost Unit
Zovirax 200 mg/5ml Suspension 473ml Bottle 264.95 USD bottle
Zovirax 5% Ointment 15 gm Tube 191.56 USD tube
Zovirax 5% Cream 5 gm Tube 165.07 USD tube
Zovirax 5% Cream 2 gm Tube 69.44 USD tube
Zovirax 5% cream 30.22 USD g
Zovirax 800 mg tablet 11.83 USD tablet
Zovirax 400 mg tablet 6.09 USD tablet
Zovirax 800 mg Tablet 5.71 USD tablet
Acyclovir 800 mg tablet 3.81 USD tablet
Zovirax 200 mg capsule 3.08 USD capsule
Acyclovir 800 mg Tablet 2.99 USD tablet
Apo-Acyclovir 800 mg Tablet 2.99 USD tablet
Mylan-Acyclovir 800 mg Tablet 2.99 USD tablet
Novo-Acyclovir 800 mg Tablet 2.99 USD tablet
Nu-Acyclovir 800 mg Tablet 2.99 USD tablet
Ratio-Acyclovir 800 mg Tablet 2.99 USD tablet
Zovirax 400 mg Tablet 2.9 USD tablet
Acyclovir 400 mg tablet 2.26 USD tablet
Acyclovir 400 mg Tablet 1.63 USD tablet
Apo-Acyclovir 400 mg Tablet 1.63 USD tablet
Mylan-Acyclovir 400 mg Tablet 1.63 USD tablet
Novo-Acyclovir 400 mg Tablet 1.63 USD tablet
Nu-Acyclovir 400 mg Tablet 1.63 USD tablet
Ratio-Acyclovir 400 mg Tablet 1.63 USD tablet
Zovirax 200 mg Tablet 1.44 USD tablet
Acyclovir 200 mg capsule 1.01 USD capsule
Acyclovir 200 mg Tablet 0.81 USD tablet
Apo-Acyclovir 200 mg Tablet 0.81 USD tablet
Mylan-Acyclovir 200 mg Tablet 0.81 USD tablet
Novo-Acyclovir 200 mg Tablet 0.81 USD tablet
Ratio-Acyclovir 200 mg Tablet 0.81 USD tablet
Acyclovir 200 mg/5ml Suspension 0.3 USD ml
Zovirax 40 mg/ml Suspension 0.28 USD ml
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Patents
Country Patent Number Approved Expires (estimated)
Canada 2098108 2001-07-03 2012-01-29
Properties
State solid
Experimental Properties
Property Value Source
melting point 255 °C PhysProp
water solubility 1620 mg/L (at 22 °C) KRISTL,A ET AL. (1993)
logP -1.56 KRISTL,A ET AL. (1993)
Caco2 permeability -6.15 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 9.08e+00 g/l ALOGPS
logP -0.95 ALOGPS
logP -1 ChemAxon
logS -1.4 ALOGPS
pKa (strongest acidic) 7.99 ChemAxon
pKa (strongest basic) 2.63 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 114.76 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 54.63 ChemAxon
polarizability 21.51 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. 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
External Links
Resource Link
KEGG Drug D00222 Link_out
KEGG Compound C06810 Link_out
PubChem Compound 2022 Link_out
PubChem Substance 46506002 Link_out
ChemSpider 1945 Link_out
ChEBI 2453 Link_out
ChEMBL 2453 Link_out
Therapeutic Targets Database DNC000157 Link_out
PharmGKB PA448045 Link_out
HET AC2 Link_out
Drug Product Database 2242784 Link_out
RxList http://www.rxlist.com/cgi/generic/acyclo.htm Link_out
Drugs.com http://www.drugs.com/acyclovir.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Aciclovir Link_out
ATC Codes
  • D06BB03
  • J05AB01
  • S01AD03
  • J05AB11
AHFS Codes
  • 84:04.06
  • 08:18.32
PDB Entries
FDA label Not Available
MSDS show (37 KB)
Interactions
Drug Interactions
Drug Interaction
Aminophylline Acyclovir increases the effect and toxicity of theophylline
Dyphylline Acyclovir increases the effect and toxicity of dyphylline.
Oxtriphylline Aciclovir may increase the effect and toxicity of oxtriphylline.
Theophylline Acyclovir may increase the effect and toxicity of theophylline.
Food Interactions
  • Increase liquid intake.
  • Take without regard to meals.
Targets

1. Thymidine kinase

Pharmacological action: yes
Actions: potentiator

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 their genome

Organism class: viral
UniProt ID: P03176 Link_out
Gene: TK
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

2. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P04293 Link_out
Gene: UL30
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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. 2007 Sep 17;. Pubmed
  4. 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
  5. 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

3. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P09252 Link_out
Gene: ORF28
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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. 2007 Sep 17;. Pubmed
  4. 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
  5. 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
Transporters

1. Solute carrier family 22 member 1

Actions: inhibitor

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-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

2. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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

3. Solute carrier family 22 member 8

Actions: substrate, inhibitor

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, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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

4. Ileal sodium/bile acid cotransporter

Actions: substrate

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

UniProt ID: Q12908 Link_out
Gene: SLC10A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19