Enfuvirtide, a peptide-based anti-HIV-1 fusion inhibitor, is an approved antiviral medication that prevents human immunodeficiency virus (HIV) from infecting healthy cells in the body. It has poor oral systemic availability and is given subcu-taneously. Enfuvirtide is used together with other medications to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Enfuvirtide is a linear 36-amino acid synthetic peptide with the N-terminus acetylated and the C-terminus is a carboxamide. It is composed of naturally occurring L-amino acid residues. Enfuvirtide is a white to off-white amorphous solid.
Physicochemical Properties
| Molecular Formula | C204H301N51O64 |
| Molecular Weight | 4491.87603999996 |
| Exact Mass | 4489.19 |
| Elemental Analysis | C, 54.55; H, 6.75; N, 15.90; O, 22.79 |
| CAS # | 159519-65-0 |
| Related CAS # | Enfuvirtide acetate;914454-00-5 |
| Appearance | White to off-white solid powder |
| Density | 1.59g/cm3 |
| LogP | 5.697 |
| InChi Key | PEASPLKKXBYDKL-FXEVSJAOSA-N |
| Synonyms | Enfuvirtide; DP178; DP-178; DP 178 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | HIV-1 |
| ln Vitro | According to a cell-cell fusion assay, 23 ± 6 nM is the effective concentration required to achieve 50% inhibition (IC50) of enfuvirtide[2]. The expression of the HIV p24 antigen and the Gag gene in macrophages is significantly inhibited by IFN-λs (1, 2, or 3) or antiretrovirals (AZT, Efavirenz, Indinavir, and Enfuvirtide). The anti-HIV (Bal) effects of AZT, Efavirenz, Indinavir, and Enfuvirtide were also improved by IFN-λs (1, 2, or 3)[3]. |
| ln Vivo | Enfuvirtide has a T1/2 of 3.8 h[2]. |
| Animal Protocol | Seven days after being cultured (105 cells/well in 96-well plates), the macrophages are incubated with or without IFN-λ1, λ2, or λ3 (100 ng/mL each) and/or anti-HIV medications for 24 hours. These medications include Azidothymidine (AZT) 10 pM, Efavirenz 100 pM, Indinavir 10-3 pM, and Enfuvirtide 10 nM. Following that, cells are infected for two hours with various HIV strains (6 ng p24/well). Following three rounds of basic DMEM washing, cells are cultivated in new 10% DMEM supplemented with IFN-λs and/or antiretroviral medications.Day 8 post-infection is when culture supernatant for HIV Bal infection is collected for RT and p24 assays. The controls were untreated and infected cells. On day eight after infection, the expression of the HIV Gag gene in infected cells is also analyzed. At days 3, 5, 7, and 10 after infection, the culture supernatant is collected for HIV p24 protein analysis by ELISA in order to detect the anti-HIV drug-resistant virus (A012 G691-6 or TC49). Every two to three days, the cell cultures are swapped out for fresh media supplemented with IFN-λ1, λ2, or λ3 and/or antiretrovirals. The RT assay is additionally performed on the culture supernatant that was obtained on day 10 postinfection[3]. |
| References |
[1]. Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance. Sci Rep. 2017 Mar 30;7:45647. [2]. The improved efficacy of Sifuvirtide compared with Enfuvirtide might be related to its selectivity for the rigid biomembrane, as determined through surface plasmon resonance. PLoS One. 2017 Feb 16;12(2):e0171567. [3]. IFN-λ Inhibits Drug-Resistant HIV Infection of Macrophages. Front Immunol. 2017 Mar 6;8:210. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~20 mg/mL (~4.45 mM) H2O : ~0.67 mg/mL (~0.15 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (0.45 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 20.0 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 mg/mL (0.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2226 mL | 1.1131 mL | 2.2262 mL | |
| 5 mM | 0.0445 mL | 0.2226 mL | 0.4452 mL | |
| 10 mM | 0.0223 mL | 0.1113 mL | 0.2226 mL |