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| Targets |
Sifuvirtide targets the HIV-1 envelope glycoprotein gp41, specifically the N-terminal heptad repeat (NHR) region. By binding to the NHR, sifuvirtide prevents the formation of the six-helix bundle (6-HB) that is essential for viral fusion with the host cell membrane. Unlike enfuvirtide, which is believed to act by a different mechanism, sifuvirtide efficiently blocks six-helix bundle formation in a dominant negative fashion. This mechanism allows sifuvirtide to be effective against T20-resistant HIV-1 strains.
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| ln Vitro |
Sifuvirtide exhibits high potency against a wide range of primary and laboratory-adapted HIV-1 isolates from multiple genotypes (R5 and X4 phenotypes). The effective concentration that inhibits 50% viral replication (EC₅0) is comparable to or lower than enfuvirtide (T20) and zidovudine (AZT). Importantly, sifuvirtide is highly effective against T20-resistant strains. The cytotoxic concentration causing 50% cell death (CC₅0) is relatively high, indicating a favorable selectivity index. The peptide inhibits HIV-1-mediated cell-cell fusion in a dose-dependent manner.
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| ln Vivo |
In vivo, sifuvirtide has completed Phase Ia clinical studies in 60 healthy individuals, demonstrating good safety, tolerability, and pharmacokinetic profiles. A single subcutaneous dose regimen (5, 10, 20, 30, 40 mg) was well-tolerated without serious adverse events. In HIV-infected patients, sifuvirtide (10-20 mg SC q.d.) showed improved clinical pharmacokinetics compared to enfuvirtide, with longer half-life and different characteristics between treatment-naive and treatment-experienced patients. The peptide is not yet FDA-approved but is a promising candidate for HIV/AIDS therapy.
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| Enzyme Assay |
Sifuvirtide is not a standard enzyme inhibitor; its activity is assessed by cell-cell fusion inhibition assays and viral replication assays. For fusion inhibition assays, HIV-1-infected cells (e.g., H9/HIV-1IIIB) are co-cultured with uninfected target cells (e.g., MT-2) in the presence of varying concentrations (0.01-1000 nM) of sifuvirtide. After 2-4 h, syncytium formation (multinucleated giant cells) is scored by microscopy. The EC₅0 is calculated. For viral replication assays, MT-2 or PBMCs are infected with HIV-1 (e.g., IIIB, NL4-3, primary isolates) at an MOI of 0.001-0.01. Sifuvirtide (0.1-1000 nM) is added, and p24 antigen production is measured by ELISA after 4-7 days. The EC₅0 is calculated. For six-helix bundle formation inhibition assays, purified NHR and CHR peptides are mixed in the presence or absence of sifuvirtide, and six-helix bundle formation is assessed by native PAGE or CD spectroscopy.
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| Cell Assay |
GST-pull down assays are used to confirm that sifuvirtide is a fusion inhibitor. GST-fusion proteins containing the NHR region of gp41 are immobilized on glutathione beads. Sifuvirtide is added, and binding is assessed by Western blotting using an anti-sifuvirtide antibody. For cytotoxicity, MT-2, PBMC, or H9 cells are treated with sifuvirtide (0.1-1000 nM) for 48-72 h, and viability is measured by MTT or trypan blue exclusion. The CC₅0 is calculated. Resistance studies: HIV-1 (IIIB) is passaged in the presence of increasing concentrations of sifuvirtide (0.1-10 uM) for several months, and resistant variants are sequenced to identify mutations in gp41. Cross-resistance with enfuvirtide is assessed.
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| Animal Protocol |
Phase Ia clinical study in healthy volunteers: 60 healthy individuals (n=10/dose group) received a single subcutaneous injection of sifuvirtide at doses of 5, 10, 20, 30, or 40 mg (or placebo) at abdominal sites. Safety and tolerability were monitored. Blood samples were collected for PK analysis at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 h post-dose. Sifuvirtide was well-tolerated without serious adverse events. In HIV-infected patients (treatment-naive and treatment-experienced), sifuvirtide (10-20 mg SC q.d.) was administered for 28-168 days. Blood samples were collected for PK analysis, and viral load (HIV-1 RNA copies/mL) was monitored. Sifuvirtide showed improved clinical pharmacokinetics compared to enfuvirtide.
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| ADME/Pharmacokinetics |
In healthy volunteers, sifuvirtide (5-40 mg, SC) showed a dose-proportional increase in Cmax and AUC. The decay half-life (t½) was 20.0 +/- 8.6 h (single dose) and 26.0 +/- 7.9 h (multiple dose). In treatment-naive HIV patients (10 mg q.d.), t½ was 17.8 +/- 3.7 h; in treatment-naive patients (20 mg q.d.), t½ was 39.0 +/- 3.5 h; in treatment-experienced patients (20 mg q.d. with HAART), t½ was 6.71 +/- 2.17 h. Cmax after last dose was 498 +/- 54 ng/mL (10 mg) and 897 +/- 136 ng/mL (20 mg). Compared to enfuvirtide (t½ ~3.8 h), sifuvirtide has a markedly longer half-life, possibly due to accumulation near the fusion site leading to slower clearance.
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| Toxicity/Toxicokinetics |
Sifuvirtide has low cytotoxicity (high CC₅0). In Phase Ia clinical studies in 60 healthy individuals, sifuvirtide was well-tolerated without serious adverse events. Injection site reactions (e.g., pain, erythema) were the most common adverse effects, similar to enfuvirtide. No significant laboratory abnormalities were reported. In HIV-infected patients, sifuvirtide was generally well-tolerated with no drug-related serious adverse events. However, cross-resistance between sifuvirtide and enfuvirtide has been observed. For research use, standard safety precautions for handling peptides apply: use PPE (gloves, lab coat, safety goggles), work in a fume hood, avoid inhalation and skin contact.
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| References | |
| Additional Infomation |
Sifuvirtide acetate is a research-grade second-generation HIV-1 fusion inhibitor peptide. It is not an FDA-approved drug (enfuvirtide (Fuzeon) is the only approved fusion inhibitor). Sifuvirtide has completed Phase Ia clinical studies and has been evaluated in HIV-infected patients. It is a promising candidate for treating HIV-1 infections, including those resistant to enfuvirtide. For research use only, not for diagnostic or therapeutic applications without regulatory approval. Storage: powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month.
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| Molecular Formula |
C203H309N59O72.XC2H4O2
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| Molecular Weight |
4727.98 (free base)
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| Related CAS # |
Sifuvirtide;857094-21-4
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| Appearance |
Solid powder
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| Synonyms |
SFT acetate
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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) |
H2O : ~9.09 mg/mL (~adjust pH to 12 with 1 M NaOH)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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