Peramivir

Identification

Name
Peramivir
Accession Number
DB06614  (EXPT00645, DB03655)
Type
Small Molecule
Groups
Approved, Investigational
Description

Peramivir is an experimental antiviral drug being developed by Biocryst Pharmaceuticals to treat influenza A/B. The development of peramivir is supported by the US Department of Health and Human Services as part of the government's effort to prepare for a flu pandemic. The drug has had a long history. An oral formulation was abandoned by Johnson and Johnson due to poor bioavailability. BioCryst is now developing a injectable version, in partnership with Green Cross Pharmaceuticals in South Korea and with Shionogi Pharmaceuticals in Japan. The drug is in Phase II studies.

Structure
Thumb
Synonyms
  • Peramivir anhydrous
External IDs
RWJ 270201 / RWJ-270201 / RWJ270201
Product Ingredients
IngredientUNIICASInChI Key
Peramivir hydrateQW7Y7ZR15U1041434-82-5RFUCJKFZFXNIGB-ZBBHRWOZSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RapivabSolution10 mgIntravenousBiocryst Pharmaceuticals IncNot applicableNot applicableCanada
RapivabSolution600 mg/60mLIntravenousbioCSL Inc.2014-12-20Not applicableUs
Categories
UNII
9ZS94HQO3B
CAS number
330600-85-6
Weight
Average: 328.4072
Monoisotopic: 328.211055404
Chemical Formula
C15H28N4O4
InChI Key
XRQDFNLINLXZLB-CKIKVBCHSA-N
InChI
InChI=1S/C15H28N4O4/c1-4-8(5-2)12(18-7(3)20)11-10(19-15(16)17)6-9(13(11)21)14(22)23/h8-13,21H,4-6H2,1-3H3,(H,18,20)(H,22,23)(H4,16,17,19)/t9-,10+,11+,12-,13+/m0/s1
IUPAC Name
(1S,2S,3R,4R)-4-carbamimidamido-3-[(1S)-1-acetamido-2-ethylbutyl]-2-hydroxycyclopentane-1-carboxylic acid
SMILES
[H][C@@]1([C@@H](NC(C)=O)C(CC)CC)[C@H](O)[C@H](C[C@H]1NC(N)=N)C(O)=O

Pharmacology

Indication

Investigated for use/treatment in influenza.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells.

TargetActionsOrganism
UNeuraminidaseNot AvailableInfluenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
UNeuraminidaseNot AvailableInfluenza A virus (strain A/Bangkok/1/1979 H3N2)
UNeuraminidaseNot AvailableInfluenza B virus (strain B/Beijing/1/1987)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Influenza A virus
  • Influenza B virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Influenza Vaccine (Live/Attenuated)The therapeutic efficacy of Influenza Vaccine (Live/Attenuated) can be decreased when used in combination with Peramivir.
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Varicella Zoster Vaccine (Live/Attenuated) can be decreased when used in combination with Peramivir.
Food Interactions
Not Available

References

General References
  1. Bantia S, Arnold CS, Parker CD, Upshaw R, Chand P: Anti-influenza virus activity of peramivir in mice with single intramuscular injection. Antiviral Res. 2006 Jan;69(1):39-45. Epub 2005 Nov 21. [PubMed:16325932]
External Links
PubChem Compound
154234
PubChem Substance
175427078
ChemSpider
135903
BindingDB
5024
ChEBI
85202
ChEMBL
CHEMBL139367
HET
BCZ
Wikipedia
Peramivir
AHFS Codes
  • 08:18.28 — Neuraminidase Inhibitors
PDB Entries
1l7f / 1l7g / 1l7h / 2f10 / 2htu / 3k37 / 3k39 / 4mwv / 4mx0

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentFlu caused by Influenza1
1, 2WithdrawnTreatmentFlu caused by Influenza1
2CompletedTreatmentAcute, Uncomplicated Human Influenza1
2CompletedTreatmentFlu caused by Influenza2
2, 3CompletedTreatmentFlu caused by Influenza1
3CompletedTreatmentCoughing / Headaches / Muscle Soreness / Nasal Stuffiness / Seasonal Influenza / Throat Pain / Tiredness1
3CompletedTreatmentFlu caused by Influenza1
3RecruitingTreatmentFlu caused by Influenza1
3TerminatedTreatmentCoughing / Fevers / Headaches / Nasal Stuffiness / Seasonal Influenza / Throat Pain1
3TerminatedTreatmentFlu caused by Influenza2
3WithdrawnNot AvailableFlu caused by Influenza1
4Active Not RecruitingTreatmentFlu caused by Influenza1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous10 mg
SolutionIntravenous600 mg/60mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8778997No2007-05-072027-05-07Us
US6562861No1998-12-172018-12-17Us
US6503745No1999-11-052019-11-05Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.38 mg/mLALOGPS
logP-0.27ALOGPS
logP-2.1ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)4.09ChemAxon
pKa (Strongest Basic)12.46ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area148.53 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity94.46 m3·mol-1ChemAxon
Polarizability34.85 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6611
Blood Brain Barrier+0.623
Caco-2 permeable-0.6852
P-glycoprotein substrateNon-substrate0.6498
P-glycoprotein inhibitor INon-inhibitor0.9244
P-glycoprotein inhibitor IINon-inhibitor0.852
Renal organic cation transporterNon-inhibitor0.884
CYP450 2C9 substrateNon-substrate0.7276
CYP450 2D6 substrateNon-substrate0.8204
CYP450 3A4 substrateNon-substrate0.6063
CYP450 1A2 substrateNon-inhibitor0.797
CYP450 2C9 inhibitorNon-inhibitor0.8469
CYP450 2D6 inhibitorNon-inhibitor0.9138
CYP450 2C19 inhibitorNon-inhibitor0.8338
CYP450 3A4 inhibitorNon-inhibitor0.8732
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9711
Ames testNon AMES toxic0.6544
CarcinogenicityNon-carcinogens0.8109
BiodegradationNot ready biodegradable0.6663
Rat acute toxicity2.5219 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9958
hERG inhibition (predictor II)Non-inhibitor0.9672
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Gamma amino acids and derivatives
Alternative Parents
Beta hydroxy acids and derivatives / Cyclopentanols / Acetamides / Secondary carboxylic acid amides / Guanidines / Cyclic alcohols and derivatives / Propargyl-type 1,3-dipolar organic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Carboximidamides
show 4 more
Substituents
Gamma amino acid or derivatives / Beta-hydroxy acid / Cyclopentanol / Hydroxy acid / Cyclic alcohol / Acetamide / Carboxamide group / Guanidine / Secondary alcohol / Secondary carboxylic acid amide
show 15 more
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
guanidines, acetamides, 3-hydroxy monocarboxylic acid, cyclopentanols (CHEBI:85202)

Targets

Kind
Protein
Organism
Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
Pharmacological action
Unknown
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...
Gene Name
NA
Uniprot ID
P03472
Uniprot Name
Neuraminidase
Molecular Weight
52468.405 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Influenza A virus (strain A/Bangkok/1/1979 H3N2)
Pharmacological action
Unknown
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...
Gene Name
NA
Uniprot ID
P06818
Uniprot Name
Neuraminidase
Molecular Weight
52140.54 Da
References
  1. Bantia S, Arnold CS, Parker CD, Upshaw R, Chand P: Anti-influenza virus activity of peramivir in mice with single intramuscular injection. Antiviral Res. 2006 Jan;69(1):39-45. Epub 2005 Nov 21. [PubMed:16325932]
Kind
Protein
Organism
Influenza B virus (strain B/Beijing/1/1987)
Pharmacological action
Unknown
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...
Gene Name
NA
Uniprot ID
P27907
Uniprot Name
Neuraminidase
Molecular Weight
51429.21 Da
References
  1. Bantia S, Arnold CS, Parker CD, Upshaw R, Chand P: Anti-influenza virus activity of peramivir in mice with single intramuscular injection. Antiviral Res. 2006 Jan;69(1):39-45. Epub 2005 Nov 21. [PubMed:16325932]

Drug created on March 19, 2008 10:41 / Updated on November 14, 2018 12:54