Tenofovir alafenamide hemifumarate |
Catalog No.GC37759
One-Click Copy Product Info
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Tenofovir alafenamide hemifumarate (GS-7340 hemifumarate) is a prodrug of the HIV-1 nucleotide reverse transcriptase (RT).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1392275-56-7
Sample solution is provided at 25 µL, 10mM.
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Tenofovir alafenamide hemifumarate (GS-7340 hemifumarate) is a prodrug of the HIV-1 nucleotide reverse transcriptase (RT)[1]. Tenofovir alafenamide hemifumarate is converted into the active metabolite tenofovir-diphosphate (TFV-DP) in vivo by carboxylate esterase-1 (CES1) in hepatocytes and subsequent phosphorylation[2]. TFV-DP competitively inhibits viral RT and acts as a chain terminator by incorporating into nascent viral DNA, thereby blocking HIV-1 replication[3]. Tenofovir alafenamide hemifumarate is commonly used in antiviral research against HIV-1 and HBV[4].
In vitro, treatment of MT-2 cells with Tenofovir alafenamide hemifumarate(0.01nM-1µM; 5 days)showed potent antiviral activity in vitro with EC50 values of 5nM[5].
In vivo, Tenofovir alafenamide hemifumarate (10μg/kg/day; subcutaneous implant; 12 weeks) induced severe local inflammation and necrosis in the peri-implant tissue of rhesus macaques[6]. Tenofovir alafenamide hemifumarate (0-1000mg/kg/day; 28 days; subcutaneous infusion) resulted in increased incidence and severity of fibrosis and mononuclear cell inflammation at the infusion site in male rats[7].
References:
[1] Gibson AK, Shah BM, Nambiar PH, Schafer JJ. Tenofovir Alafenamide. Ann Pharmacother. 2016;50(11):942-952.
[2] Birkus G, Bam RA, Willkom M, et al. Intracellular Activation of Tenofovir Alafenamide and the Effect of Viral and Host Protease Inhibitors. Antimicrob Agents Chemother. 2015;60(1):316-322.
[3] Uglietti A, Zanaboni D, Gnarini M, Maserati R. Emtricitabine/tenofovir in the treatment of HIV infection: current PK/PD evaluation. Expert Opin Drug Metab Toxicol. 2012;8(10):1305-1314.
[4] Hong X, Cai Z, Zhou F, et al. Improved pharmacokinetics of tenofovir ester prodrugs strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism in preclinical models. Front Pharmacol. 2022;13:932934.
[5] Callebaut C, Stepan G, Tian Y, Miller MD. In Vitro Virology Profile of Tenofovir Alafenamide, a Novel Oral Prodrug of Tenofovir with Improved Antiviral Activity Compared to That of Tenofovir Disoproxil Fumarate. Antimicrob Agents Chemother. 2015;59(10):5909-5916.
[6] Su JT, Simpson SM, Sung S, et al. A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques. Antimicrob Agents Chemother. 2020;64(3):e01893-19.
[7] Zane D, Roller S, Shelton J, et al. A 28-Day Toxicity Study of Tenofovir Alafenamide Hemifumarate by Subcutaneous Infusion in Rats and Dogs. Microbiol Spectr. 2021;9(1):e0033921.
| Cell experiment [1]: | |
Cell lines | MT-2 cells |
Preparation Method | MT-2 cells (2.4 million) were incubated with virus for 3h at 37˚C in 1mL screw-cap tubes. Virus was normalized to yield a signal-to-noise ratio (uninfected cells to infected cells) between 4 to 7, which was equivalent to a multiplicity of infection (MOI) ~0.003 for wild-type HIV-1 IIIB. Five-fold Tenofovir alafenamide hemifumarate gradient dilutions (0.01nM-1µM) were transferred in triplicate to the inside wells of 96-well plates (50µL per well). After incubation, infected MT-2 cells were seeded at 8500 per well in 100µL of media. After incubation for 5 days at 37˚C, 100µL of CellTiterGlo reagent was added to each well of the assay plates and luminescence was measured using an Envision plate reader. |
Reaction Conditions | 0.01nM-1µM; 5 days |
Applications | Treatment of MT-2 cells with Tenofovir alafenamide hemifumarate showed potent antiviral activity in vitro with EC50 values of 5nM. |
| Animal experiment [2]: | |
Animal models | Naive Male Sprague-Dawley rats |
Preparation Method | Naive male Sprague-Dawley rats were singly housed in polycarbonate caging with free access to food and water for the duration of the study, unless otherwise noted. At the time of dose initiation, animals were 11 to 14 weeks old and weighed between 372 and 549g. After an acclimation period of at least 7 days, rats were surgically implanted with a s.c. cannula while under isoflurane anesthesia. Cannulas were routed dorsally through the s.c. tissue extending from the lumbar region to an exteriorization site at the base of the neck. The cannulas were tethered through a swivel system outside the cage, and jackets were placed on the rats to hold the tethered system in place. Saline infusions were maintained at a rate of 0.04ml/h until study initiation, which occurred after a recovery period of at least 10 days. Prior to study initiation, animals were assigned to groups by a stratified randomization scheme designed to achieve similar group mean body weights. The study consisted of five treatment groups, with each group receiving Tenofovir alafenamide hemifumarate at a dose of 0, 30, 100, 300, or 1,000mg/kg/day. Within each treatment group, five animals were assigned to the main study group, and six animals were assigned to the recovery group. Each treatment group also contained two separate satellite groups: one group of six animals for Histopathology analysis and one group of eighteen animals for PBMC sample collection. |
Dosage form | 0-1000mg/kg/day; 28 days; subcutaneous infusion |
Applications | Tenofovir alafenamide hemifumarate resulted in increased incidence and severity of fibrosis and mononuclear cell inflammation at the infusion site in male rats. |
References: | |
| Cas No. | 1392275-56-7 | SDF | |
| Canonical SMILES | O=C(O)/C=C/C(O)=O.NC1=NC=NC2=C1N=CN2C[C@@H](C)OC[P@](OC3=CC=CC=C3)(N[C@@H](C)C(OC(C)C)=O)=O.[0.5] | ||
| Formula | C21H29N6O5P.1/2 C4H4O4 | M.Wt | 534.5 |
| Solubility | DMSO: 50 mg/mL (93.55 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8709 mL | 9.3545 mL | 18.7091 mL |
| 5 mM | 374.2 μL | 1.8709 mL | 3.7418 mL |
| 10 mM | 187.1 μL | 935.5 μL | 1.8709 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)