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Identification
NameZanamivir
Accession NumberDB00558  (APRD00378)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionA guanido-neuraminic acid that is used to inhibit neuraminidase. [PubChem]
Structure
Thumb
Synonyms
(2R,3R,4S)-3-(acetylamino)-4-Carbamimidamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid
4-Guanidino-neu5ac2en
5-(acetylamino)-2,6-Anhydro-4-carbamimidamido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid
5-acetamido-2,6-Anhydro-3,4,5-trideoxy-4-guanidino-D-glycero-D-galacto-non-2-enonic acid
GANA
GNA
Modified sialic acid
Relenza
Zanamavir
ZANAMIVIR
ZMR
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RelenzaPowder5 mg/1Respiratory (inhalation)Physicians Total Care, Inc.2009-01-20Not applicableUs
RelenzaPowder5 mg/1Respiratory (inhalation)Dispensing Solutions Inc.2002-12-22Not applicableUs
RelenzaPowder5 mgOral; Respiratory (inhalation)Glaxosmithkline Inc1999-12-07Not applicableCanada
RelenzaPowder5 mg/1Respiratory (inhalation)Glaxo Smith Kline Llc1999-09-22Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIL6O3XI777I
CAS number139110-80-8
WeightAverage: 332.3098
Monoisotopic: 332.133199014
Chemical FormulaC12H20N4O7
InChI KeyARAIBEBZBOPLMB-UFGQHTETSA-N
InChI
InChI=1S/C12H20N4O7/c1-4(18)15-8-5(16-12(13)14)2-7(11(21)22)23-10(8)9(20)6(19)3-17/h2,5-6,8-10,17,19-20H,3H2,1H3,(H,15,18)(H,21,22)(H4,13,14,16)/t5-,6+,8+,9+,10+/m0/s1
IUPAC Name
(2R,3R,4S)-4-[(diaminomethylidene)amino]-3-acetamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
SMILES
[H][C@]1(OC(=C[[email protected]](N=C(N)N)[[email protected]]1NC(C)=O)C(O)=O)[[email protected]](O)[[email protected]](O)CO
Pharmacology
IndicationFor the prevention and treatment of influenza A and B.
Structured Indications
PharmacodynamicsZanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir.
Mechanism of actionThe proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. By binding and inhibiting the neuraminidase protein, the drug renders the influenza virus unable to escape its host cell and infect others.
TargetKindPharmacological actionActionsOrganismUniProt ID
NeuraminidaseProteinyes
inhibitor
Influenza A virus (strain A/Bangkok/1/1979 H3N2)P06818 details
NeuraminidaseProteinyes
inhibitor
Influenza B virus (strain B/Beijing/1/1987)P27907 details
Sialidase-2Proteinunknown
inhibitor
HumanQ9Y3R4 details
Related Articles
AbsorptionAbsolute bioavailability is very low following oral administration (2%). Following oral inhalation, bioavailability is 4% to 17%.
Volume of distributionNot Available
Protein bindingZanamivir has limited plasma protein binding (<10%).
Metabolism

Not metabolized

Route of eliminationIt is excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Unabsorbed drug is excreted in the feces.Zanamivir is renally excreted as unchanged drug.
Half life2.5-5.1 hours
Clearance
  • 2.5 – 10.9 L/h [Following oral inhalation 10 mg]
  • 5.3 L/h [Normal renal function receiving IV single dose of 4 mg or 2 mg]
  • 2.7 L/h [Patients with mild and moderate renal impairement receiving IV single dose of 4 mg or 2 mg]
  • 0.8 L/h [Patients with severe renal impairement receiving IV single dose of 4 mg or 2 mg]
ToxicityNot Available
Affected organisms
  • Influenza A virus
  • Influenza B virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis Reference

Manjinder Singh Phull, Rajendra Narayanrao Kankan, Dharmaraj Ramachandra Rao, Ashwini Amol Sawant, Sanoj Thoppil, “Process for Preparing Zanamivir and Intermediates for Use in the Process.” U.S. Patent US20110257418, issued October 20, 2011.

US20110257418
General References
  1. Meindl P, Bodo G, Palese P, Schulman J, Tuppy H: Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology. 1974 Apr;58(2):457-63. [PubMed:4362431 ]
  2. von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, et al.: Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature. 1993 Jun 3;363(6428):418-23. [PubMed:8502295 ]
  3. Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T: Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. Antimicrob Agents Chemother. 2008 Oct;52(10):3484-91. doi: 10.1128/AAC.00344-08. Epub 2008 Aug 11. [PubMed:18694948 ]
  4. Sugaya N, Tamura D, Yamazaki M, Ichikawa M, Kawakami C, Kawaoka Y, Mitamura K: Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. 2008 Aug 1;47(3):339-45. doi: 10.1086/589748. [PubMed:18582202 ]
External Links
ATC CodesJ05AH01
AHFS Codes
  • 08:18.28
PDB Entries
FDA labelDownload (36.7 KB)
MSDSDownload (53.6 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8406
Blood Brain Barrier-0.8899
Caco-2 permeable-0.7094
P-glycoprotein substrateSubstrate0.5497
P-glycoprotein inhibitor INon-inhibitor0.8288
P-glycoprotein inhibitor IINon-inhibitor0.9701
Renal organic cation transporterNon-inhibitor0.9405
CYP450 2C9 substrateNon-substrate0.7868
CYP450 2D6 substrateNon-substrate0.8139
CYP450 3A4 substrateNon-substrate0.6779
CYP450 1A2 substrateNon-inhibitor0.8684
CYP450 2C9 inhibitorNon-inhibitor0.8942
CYP450 2D6 inhibitorNon-inhibitor0.9262
CYP450 2C19 inhibitorNon-inhibitor0.8727
CYP450 3A4 inhibitorNon-inhibitor0.9647
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9903
Ames testNon AMES toxic0.5316
CarcinogenicityNon-carcinogens0.9226
BiodegradationReady biodegradable0.6996
Rat acute toxicity2.1565 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9827
hERG inhibition (predictor II)Non-inhibitor0.9528
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
Packagers
Dosage forms
FormRouteStrength
PowderOral; Respiratory (inhalation)5 mg
PowderRespiratory (inhalation)5 mg/1
Prices
Unit descriptionCostUnit
Relenza Diskhaler 20 5 mg/blister Aerosol Inhaler75.73USD inhaler
Relenza 5 mg diskhaler3.54USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2081356 No2000-02-222011-04-24Canada
CA2291994 No2003-10-142011-04-24Canada
US5360817 No1993-07-262013-07-26Us
US6294572 No1994-12-152014-12-15Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP-3Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.31 mg/mLALOGPS
logP-2.3ALOGPS
logP-5.8ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)3.25ChemAxon
pKa (Strongest Basic)11.93ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area200.72 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity76.19 m3·mol-1ChemAxon
Polarizability31.24 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyranoid amino acids and derivatives. These are compounds containing a (hydro)pyran ring bearing unprotected amino and carboxylic acid functionalities.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassSugar acids and derivatives
Direct ParentPyranoid amino acids and derivatives
Alternative Parents
Substituents
  • Pyranoid amino acid
  • Acetamide
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Polyol
  • Guanidine
  • Carboxamide group
  • 1,2-diol
  • Oxacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Influenza A virus (strain A/Bangkok/1/1979 H3N2)
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of th...
Gene Name:
NA
Uniprot ID:
P06818
Molecular Weight:
52140.54 Da
References
  1. Macdonald SJ, Cameron R, Demaine DA, Fenton RJ, Foster G, Gower D, Hamblin JN, Hamilton S, Hart GJ, Hill AP, Inglis GG, Jin B, Jones HT, McConnell DB, McKimm-Breschkin J, Mills G, Nguyen V, Owens IJ, Parry N, Shanahan SE, Smith D, Watson KG, Wu WY, Tucker SP: Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza. J Med Chem. 2005 Apr 21;48(8):2964-71. [PubMed:15828835 ]
  2. Murrell MT, Porotto M, Greengard O, Poltoratskaia N, Moscona A: A single amino acid alteration in the human parainfluenza virus type 3 hemagglutinin-neuraminidase glycoprotein confers resistance to the inhibitory effects of zanamivir on receptor binding and neuraminidase activity. J Virol. 2001 Jul;75(14):6310-20. [PubMed:11413297 ]
  3. Mungall BA, Xu X, Klimov A: Assaying susceptibility of avian and other influenza A viruses to zanamivir: comparison of fluorescent and chemiluminescent neuraminidase assays. Avian Dis. 2003;47(3 Suppl):1141-4. [PubMed:14575130 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Influenza B virus (strain B/Beijing/1/1987)
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of th...
Gene Name:
NA
Uniprot ID:
P27907
Molecular Weight:
51429.21 Da
References
  1. Eiland LS, Eiland EH: Zanamivir for the prevention of influenza in adults and children age 5 years and older. Ther Clin Risk Manag. 2007 Jun;3(3):461-5. [PubMed:18488077 ]
  2. Oakley AJ, Barrett S, Peat TS, Newman J, Streltsov VA, Waddington L, Saito T, Tashiro M, McKimm-Breschkin JL: Structural and functional basis of resistance to neuraminidase inhibitors of influenza B viruses. J Med Chem. 2010 Sep 9;53(17):6421-31. doi: 10.1021/jm100621s. [PubMed:20695427 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Exo-alpha-(2->8)-sialidase activity
Specific Function:
Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins, oligosaccharides and gangliosides.
Gene Name:
NEU2
Uniprot ID:
Q9Y3R4
Molecular Weight:
42253.345 Da
References
  1. Chavas LM, Kato R, Suzuki N, von Itzstein M, Mann MC, Thomson RJ, Dyason JC, McKimm-Breschkin J, Fusi P, Tringali C, Venerando B, Tettamanti G, Monti E, Wakatsuki S: Complexity in influenza virus targeted drug design: interaction with human sialidases. J Med Chem. 2010 Apr 8;53(7):2998-3002. doi: 10.1021/jm100078r. [PubMed:20222714 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23