| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
HIV-1
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|---|---|
| ln Vitro |
As an ICT or DCT, EFdA-TP tetraammonium (0.05–10 μM) blocks RT-catalyzed DNA synthesis for 15 minutes[1]. As a translocation-defective RT inhibitor that significantly slows down DNA synthesis, EFdA-TP tetraammonium can block RT and function as a de facto immediate chain terminator. As a delayed chain terminator, EFdA-TP tetraammonium can include one extra dNTP before preventing DNA synthesis[1].
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| ln Vivo |
EFdA is active against wild-type (EC50 as low as 50 pmol/l) and most highly NRTI-resistant viruses. The active metabolite, EFdA-triphosphate, has been shown to have a prolonged intracellular half-life in human and rhesus (Rh) blood cells. As a result, single drug doses tested in simian immunodeficiency virus mac251-infected Rh macaques and HIV-1-infected individuals exhibited robust antiviral activity of 7-10 days duration. Preclinical studies of EFdA as preexposure prophylaxis in the Rh macaque/simian/human immunodeficiency virus low-dose intrarectal challenge model have shown complete protection when given in clinically relevant doses[1].
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| References |
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| Additional Infomation |
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a nucleoside analog. Unlike approved nucleoside reverse transcriptase inhibitors against human immunodeficiency virus type 1 (HIV-1), EFdA has a 3'-OH group and exhibits significant activity against both wild-type and drug-resistant HIV. EFdA triphosphate (EFdA-TP) is unique among nucleoside reverse transcriptase inhibitors because it inhibits HIV-1 reverse transcriptase (RT) through multiple mechanisms. (a) EFdA-TP can act as a translocation-deficient RT inhibitor, blocking RT and thus significantly slowing DNA synthesis, effectively acting as an immediate chain terminator. Although untranslocated EFdA-MP terminated primers can be unblocked, they can be efficiently converted back to their EFdA-MP terminated form. (b) EFdA-TP can act as a delayed chain terminator, allowing the incorporation of additional dNTPs before blocking DNA synthesis. In this case, EFdA-MP terminated primers are spared excision. (c) EFdA-MP can be efficiently mismatched by reverse transcriptase, making it extremely difficult for mismatched primers to extend and also avoid excision. The background of the template sequence determines the relative contribution of each mechanism and affects the affinity of EFdA-MP for potential incorporation sites, which partly explains the lack of antagonism between EFdA and tenofovir. Changes in the type of nucleotide before EFdA-MP incorporation can change its inhibitory mechanism from a delayed chain terminator to an immediate chain terminator. The multifunctionality of EFdA in inhibiting HIV replication through multiple mechanisms may explain why resistance to EFdA is more difficult to develop. [2]
Review objective: 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a nucleoside reverse transcriptase inhibitor (NRTI) with a novel mechanism of action, a unique structure, and unparalleled anti-HIV-1 activity among NRTIs. We will summarize its structure and function, antiviral activity, resistance spectrum, and potential application as an antiretroviral drug in the treatment and pre-exposure prophylaxis of HIV-1 infection. Recent findings: EFdA is effective against wild-type viruses (EC50 as low as 50 pmol/L) and most highly NRTI-resistant viruses. The active metabolite EFdA-triphosphate has a long intracellular half-life in human and rhesus monkey (Rh) hemocytes. Therefore, single-dose administration tested in rhesus monkeys infected with simian immunodeficiency virus mac251 and HIV-1 infected individuals showed potent antiviral activity lasting 7–10 days. Preclinical studies of EFdA as a pre-exposure prophylaxis drug in a low-dose rectal challenge model of rhesus monkey/monkey/human immunodeficiency virus showed that administration at clinically relevant doses provided complete protection. Summary: EFdA is a novel antiretroviral drug effective against both wild-type viruses and NRTI-resistant viruses. Due to the long intracellular half-life of its active ingredient, the dosing regimen can be flexibly adjusted, from at least once daily, once weekly, or even longer. [1] |
| Molecular Formula |
C12H27FN9O12P3
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|---|---|
| Molecular Weight |
601.32
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| Related CAS # |
EFdA-TP;950913-56-1;EFdA-TP tetrasodium;2883783-00-2
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| Appearance |
Off-white to light yellow 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6630 mL | 8.3150 mL | 16.6301 mL | |
| 5 mM | 0.3326 mL | 1.6630 mL | 3.3260 mL | |
| 10 mM | 0.1663 mL | 0.8315 mL | 1.6630 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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