Identification

Name
Enfuvirtide
Accession Number
DB00109  (BTD00106, BIOD00106)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Peptides
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 structure
Db00109
Protein chemical formula
C204H301N51O64
Protein average weight
4491.876 Da
Sequences
>DB00109 sequence
YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF
Download FASTA Format
Synonyms
Not Available
External IDs
DP-178 / DP178 / T-20 / T20
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FuzeonPowder, for solution108 mgSubcutaneousHoffmann La Roche2003-08-18Not applicableCanada
FuzeonKit90 mg/1mLGenentech, Inc.2012-04-10Not applicableUs
FuzeonInjection, powder, for solution90 mg/mlSubcutaneousRoche Registration Gmb H2003-05-27Not applicableEu
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
FuzeonEnfuvirtide + WaterKitRoche Laboratories Inc.2006-05-16Not applicableUs
Categories
UNII
19OWO1T3ZE
CAS number
159519-65-0

Pharmacology

Indication

Enfuvirtide is an antiretroviral drug used in combination therapy for the treatment of HIV-1/AIDS.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Enfuvirtide 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.

TargetActionsOrganism
AEnvelope glycoproteinNot AvailableHuman immunodeficiency virus 1
Absorption

After 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 binding

92%

Metabolism

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

Route of elimination
Not Available
Half life

3.8 +/- 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]
Toxicity
Not Available
Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
RitonavirThe serum concentration of Enfuvirtide can be increased when it is combined with Ritonavir.
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Varicella Zoster Vaccine (Live/Attenuated) can be decreased when used in combination with Enfuvirtide.
Food Interactions
Not 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
UniProt
Q70626
Genbank
U12055
PubChem Substance
46506067
ChemSpider
16743716
BindingDB
50271301
ChEMBL
CHEMBL525076
Therapeutic Targets Database
DAP000157
PharmGKB
PA164744517
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Enfuvirtide
ATC Codes
J05AX07 — Enfuvirtide
AHFS Codes
  • 08:18.08.04 — HIV Fusion Inhibitors
FDA label
Download (153 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingBasic ScienceHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections7
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Progressive Multifocal Leukoencephalopathy1
2CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
4CompletedDiagnosticCardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections8
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
Not AvailableUnknown StatusNot AvailableAntiretroviral Treatment / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
Packagers
  • F Hoffmann La Roche Ltd.
  • F Hoffmann-La Roche Ltd.
  • Gilead Sciences Inc.
  • Pharmacia Inc.
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous90 mg/ml
Kit
Kit90 mg/1mL
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)
US6475491No1995-06-072015-06-07Us
US5464933No1993-06-072013-06-07Us
CA2224008No2009-08-182016-06-06Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
hydrophobicity-0.875Not Available
isoelectric point4.30Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not 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
Uniprot Name
Envelope glycoprotein
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
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]

Drug created on June 13, 2005 07:24 / Updated on September 25, 2018 00:40