| Size | Price | Stock | Qty |
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| Targets |
HIV fusion[1]
Enfuvirtide acetate targets the HIV-1 envelope glycoprotein gp41, specifically the heptad repeat 1 (HR1) region. By binding to HR1, the peptide prevents the conformational changes required for the formation of the six-helix bundle fusion core, thereby blocking the fusion of the viral and host cell membranes. This mechanism of action is distinct from that of protease inhibitors, reverse transcriptase inhibitors, and integrase inhibitors, making enfuvirtide effective against HIV-1 strains resistant to other classes of antiretroviral drugs. The target is the viral fusion machinery rather than a host cell protein. |
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| ln Vitro |
The effective concentration required to achieve 50% inhibition (IC50) of enfuvirtide, as revealed by cell-cell fusion, is 23 ± 6 nM[2]. HIV p24 antigen and Gag gene expression in macrophages is markedly inhibited by IFN-λs (1, 2, or 3) or antiretrovirals (AZT, Efavirenz, Indinavir test, and Enfuvirtide). Additionally, AZT, Efavirenz, Indinavir, and Enfuvirtide's anti-HIV (Bal) effects are strengthened by IFN-λs (1, 2, or 3)[3].
In vitro studies demonstrate that enfuvirtide acetate is a potent inhibitor of HIV-1 fusion. A cell-cell fusion assay reveals that the effective concentration for achieving 50% inhibition (IC₅0) is 23 +/- 6 nM. The peptide exhibits activity against a broad range of HIV-1 isolates, including those resistant to other antiretroviral classes. In vitro resistance to enfuvirtide involves mutations in the gp41 HR1 region that reduce peptide binding. The compound's antiviral activity is typically assessed using HIV-1-infected cell lines or primary cells, with viral replication measured by p24 antigen production or luciferase reporter assays. |
| ln Vivo |
T1/2 for enfuvirtide is 3.8 hours[2].
In vivo, enfuvirtide acetate has demonstrated efficacy in reducing HIV-1 viral load in treatment-experienced patients. Clinical studies have shown that enfuvirtide, when used in combination with optimized background therapy, significantly reduces plasma HIV-1 RNA levels and increases CD4+ T-cell counts. The peptide's in vivo efficacy is limited by its rapid proteolytic degradation and the development of resistance mutations in gp41. It is administered via subcutaneous injection twice daily due to its poor oral bioavailability. Its clinical utility is primarily in patients with multidrug-resistant HIV-1 infection. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for enfuvirtide acetate typically involve assessing its binding to the gp41 HR1 region of HIV-1. Surface plasmon resonance (SPR) or biolayer interferometry can be used to measure the binding affinity of the peptide to synthetic HR1 peptides or recombinant gp41 constructs. Competitive binding assays using labeled enfuvirtide derivatives allow for quantification of binding inhibition by other compounds. The peptide's ability to inhibit fusion is assessed in cell-based fusion assays where HIV-1 envelope-expressing cells are co-cultured with target cells expressing CD4 and co-receptors, and fusion is quantified by reporter gene activation.
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| Cell Assay |
Cellular assays for enfuvirtide acetate involve infecting susceptible cell lines (e.g., MT-2, CEM, or primary CD4+ T cells) with HIV-1 in the presence of varying concentrations of the peptide. Cells are cultured in appropriate media at 37degC with 5% CO2, and viral replication is measured after 3-7 days using p24 antigen ELISA, reverse transcriptase activity, or luciferase reporter assays for recombinant viruses. Cytotoxicity is assessed in parallel using MTT or similar assays to ensure that observed antiviral effects are not due to cell death. IC₅0 values are calculated from dose-response curves. Resistance selection experiments are performed by passaging virus in increasing concentrations of the peptide.
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| Animal Protocol |
In vivo animal studies for enfuvirtide acetate are limited because the peptide is specifically designed to target HIV-1, which does not infect standard laboratory animals. Pharmacokinetic and toxicology studies have been conducted in animal models (rats, dogs, and monkeys) to support clinical development. These studies evaluate the compound's absorption, distribution, metabolism, and excretion following subcutaneous or intravenous administration. Efficacy studies are not feasible in animals due to the lack of HIV-1 infection models. Instead, human clinical trials have been the primary source of in vivo efficacy data, demonstrating significant antiviral activity in HIV-1-infected patients.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of enfuvirtide acetate are characterized by rapid absorption following subcutaneous injection, with a bioavailability of approximately 84%. The peptide has a half-life of approximately 3-4 hours, necessitating twice-daily dosing. It is metabolized by proteolytic degradation into amino acids, with no active metabolites. The compound is not significantly bound to plasma proteins and is eliminated via renal clearance of peptide fragments. Its molecular weight is approximately 4552 Da. Due to its peptide nature, it has poor oral bioavailability and must be administered parenterally.
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| Toxicity/Toxicokinetics |
Toxicological data for enfuvirtide acetate have been extensively characterized in preclinical and clinical studies. The compound is generally well-tolerated, with the most common adverse events being local injection site reactions (pain, erythema, induration, nodules, and cysts). Systemic adverse effects include an increased risk of bacterial pneumonia and hypersensitivity reactions. In preclinical toxicology studies, the compound showed no significant genotoxicity or carcinogenicity. It is not recommended for use in patients with a history of hypersensitivity to enfuvirtide or any of its components. The compound is FDA-approved for clinical use in HIV-1 infection.
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| References | |
| Additional Infomation |
Enfuvirtide acetate is an FDA-approved anti-HIV-1 fusion inhibitor peptide marketed under the brand name Fuzeon. It is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. The peptide was first approved by the FDA in 2003. Its mechanism of action involves binding to gp41 and blocking viral fusion. Resistance involves mutations in the gp41 HR1 region. The compound is administered by subcutaneous injection twice daily. It is supplied as a sterile, lyophilized powder for reconstitution.
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| Molecular Formula |
C206H305N51O66
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| Molecular Weight |
4551.93
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| CAS # |
914454-00-5
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| Related CAS # |
Enfuvirtide;159519-65-0
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (21.97 mM)
H2O : 2 mg/mL (0.44 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (0.55 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (0.55 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (0.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2197 mL | 1.0984 mL | 2.1969 mL | |
| 5 mM | 0.0439 mL | 0.2197 mL | 0.4394 mL | |
| 10 mM | 0.0220 mL | 0.1098 mL | 0.2197 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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