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Identification
NameEnfuvirtide
Accession NumberDB00109  (BTD00106, BIOD00106)
TypeBiotech
GroupsApproved, Investigational
Description

Enfuvirtide is a 36 residue synthetic peptide that inhibits HIV-1 fusion with CD4 cells. It is an N-terminal acetylated, C-terminal amide. As an HIV fusion inhibitor, it is the first of a novel class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection.

Protein structureDb00109
Related Articles
Protein chemical formulaC204H301N51O64
Protein average weight4491.876 Da
Sequences
>DB00109 sequence
YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF
Download FASTA Format
Synonyms
Envelope polyprotein GP160 precursor [Contains: Exterior membrane glycoprotein,GP120, Transmembrane glycoprotein,GP41]
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FuzeonkitGenentech, Inc.2012-04-10Not applicableUs
Fuzeonpowder for solution108 mgsubcutaneousHoffmann La Roche Limited2003-08-18Not applicableCanada
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
UNII19OWO1T3ZE
CAS number159519-65-0
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationEnfuvirtide is an antiretroviral drug used in combination therapy for the treatment of HIV-1/AIDS.
PharmacodynamicsNot Available
Mechanism of actionEnfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes. It works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. Enfuvirtide is a biomimetic peptide that was rationally designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion.
Related Articles
AbsorptionAfter a 90 mg single subcutaneous injection of Enfuvirtide into the abdomen in 12 HIV-1 infected subjects, the mean peak concentration is 4.59+/-1.5 ug/ml and the median time to peak concentration was 8 hours (ranged from 3 to12 hours).
Volume of distribution
  • 5.5 ± 1.1 L
Protein binding92%
Metabolism

Expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool.

Route of eliminationNot Available
Half life3.8 +/- 0.6 hrs
Clearance
  • 24.8 +/- 4.1 mL/h/kg [HIV-1 infected adult and pediatric subjects following a 90-mg single SC dose of enfuvirtide]
  • 30.6 +/- 10.6 mL/h/kg [Following 90-mg twice daily dosing of FUZEON SC in combination with other antiretroviral agents in HIV-1 infected subjects]
  • 40 +/- 17 mL/h/kg [pediatric patients in the presence of concomitant medications including antiretroviral agents receiving the 2 mg/kg twice daily dose]
ToxicityNot Available
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
Packagers
Dosage forms
FormRouteStrength
Kit
Powder for solutionsubcutaneous108 mg
Prices
Unit descriptionCostUnit
Fuzeon convenience kit3062.23USD kit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2224008 No2009-08-182016-06-06Canada
US5464933 No1993-06-072013-06-07Us
US6475491 No1995-06-072015-06-07Us
Properties
StateLiquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.875Not Available
isoelectric point4.30Not Available
References
Synthesis Reference

Ananda Kuppanna, Reddy Maria Bhaskar Reddy Komma, Debashish Datta. An improved process for the preparation of enfuvirtide. WO2011095989A2 (Issued Aug 11, 2011).

General References
  1. Greenberg ML, Cammack N: Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother. 2004 Aug;54(2):333-40. Epub 2004 Jul 1. [PubMed:15231762 ]
External Links
ATC CodesJ05AX07
AHFS Codes
  • 08:18.08.04
PDB Entries
FDA labelDownload (153 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AtazanavirThe serum concentration of Enfuvirtide can be increased when it is combined with Atazanavir.
BatimastatThe serum concentration of Enfuvirtide can be increased when it is combined with Batimastat.
DarunavirThe serum concentration of Enfuvirtide can be increased when it is combined with Darunavir.
FosamprenavirThe serum concentration of Enfuvirtide can be increased when it is combined with Fosamprenavir.
IndinavirThe serum concentration of Enfuvirtide can be increased when it is combined with Indinavir.
IsoflurophateThe serum concentration of Enfuvirtide can be increased when it is combined with Isoflurophate.
NelfinavirThe serum concentration of Enfuvirtide can be increased when it is combined with Nelfinavir.
RitonavirThe serum concentration of Enfuvirtide can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Enfuvirtide can be increased when it is combined with Saquinavir.
SimeprevirThe serum concentration of Enfuvirtide can be increased when it is combined with Simeprevir.
TipranavirThe serum concentration of Enfuvirtide can be increased when it is combined with Tipranavir.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
yes
General Function:
Structural molecule activity
Specific Function:
Not Available
Gene Name:
gp41
Uniprot ID:
Q53I07
Molecular Weight:
16767.98 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 ]
  3. Cabrera C, Marfil S, Garcia E, Martinez-Picado J, Bonjoch A, Bofill M, Moreno S, Ribera E, Domingo P, Clotet B, Ruiz L: Genetic evolution of gp41 reveals a highly exclusive relationship between codons 36, 38 and 43 in gp41 under long-term enfuvirtide-containing salvage regimen. AIDS. 2006 Oct 24;20(16):2075-80. [PubMed:17053353 ]
  4. Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, Melby T, Sista P, Erickson J, Lambert D, Stanfield-Oakley SA, Salgo M, Cammack N, Matthews T, Greenberg ML: Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol. 2005 Oct;79(19):12447-54. [PubMed:16160172 ]
  5. Aquaro S, D'Arrigo R, Svicher V, Perri GD, Caputo SL, Visco-Comandini U, Santoro M, Bertoli A, Mazzotta F, Bonora S, Tozzi V, Bellagamba R, Zaccarelli M, Narciso P, Antinori A, Perno CF: Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. J Antimicrob Chemother. 2006 Oct;58(4):714-22. Epub 2006 Aug 5. [PubMed:16891628 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Patel IH, Zhang X, Nieforth K, Salgo M, Buss N: Pharmacokinetics, pharmacodynamics and drug interaction potential of enfuvirtide. Clin Pharmacokinet. 2005;44(2):175-86. [PubMed:15656696 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Patel IH, Zhang X, Nieforth K, Salgo M, Buss N: Pharmacokinetics, pharmacodynamics and drug interaction potential of enfuvirtide. Clin Pharmacokinet. 2005;44(2):175-86. [PubMed:15656696 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23