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| Targets |
HIV-1/2 nucleotide reverse transcriptase
The primary molecular target of Tenofovir hydrate is HIV-1 reverse transcriptase (RT), a viral enzyme essential for the replication of HIV. As a nucleotide reverse transcriptase inhibitor (NRTI), Tenofovir hydrate acts as a chain terminator. It is phosphorylated to its active form, tenofovir diphosphate, which competes with the natural substrate deoxyadenosine triphosphate for incorporation into the growing viral DNA chain. Once incorporated, it causes chain termination, blocking viral DNA synthesis. The compound also inhibits hepatitis B virus polymerase. Resistance arises via substitutions in catalytic and nucleotide-binding residues that reduce drug incorporation. |
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| ln Vitro |
Tenofovir exhibits cytotoxic effects on HK-2 cell viability, as demonstrated by IC50 values in the MTT assay of 9.21 and 2.77 μM at 48 and 72 hours, respectively. Tenofovir causes HK-2 cells' ATP levels to drop. In HK-2 cells, tenofovir (3.0 to 28.8 μM) elevates protein carbonylation and oxidative stress. Moreover, tenofovir causes HK-2 cells to undergo apoptosis, and this process is brought on by mitochondrial damage[1]. The replication of R5-tropic HIV-1BaL and X4-tropic HIV-1IIIb in activated PBMCs is inhibited by tenofovir and M48U1, when formulated in 0.25% HEC. Additionally, several laboratory strains and patient-derived HIV-1 isolates are inhibited. Infection with R5-tropic HIV-1BaL is inhibited by the synergistic antiretroviral activity of M48U1 and tenofovir combined in 0.25% HEC, and this formulation is not harmful to PBMCs[2].
In vitro studies demonstrate that Tenofovir hydrate inhibits the replication of both R5-tropic HIV-1BaL and X4-tropic HIV-1IIIb in activated PBMCs, and inhibits several laboratory strains and patient-derived HIV-1 isolates. The compound shows cytotoxic effects on cell viability in HK-2 cells, with IC50 values of 9.21 and 2.77 μM at 48 and 72 h in MTT assay, respectively. Tenofovir diminishes ATP levels in HK-2 cells and increases oxidative stress and protein carbonylation. It also induces apoptosis in HK-2 cells via mitochondrial damage. The compound functions as a stable nucleotide analog, supporting viral polymerase inhibition research in diverse in vitro models. |
| ln Vivo |
When given to BLT mice (20, 50, 140, or 300 mg/kg), tenofovir Disoproxil Fumarate exhibits dose-dependent activity in response to a vaginal HIV challenge in BLT humanized mice. In BLT mice, tenofovir Disoproxil Fumarate (50, 140, or 300 mg/kg) dramatically lowers HIV transmission[3]. In woodchucks with a chronic WHV infection, tenofovir Disoproxil Fumarate (0.5, 1.5, or 5.0 mg/kg/day, p.o.) causes a dose-dependent decrease in serum viremia. The administration of tenofovir Disoproxil Fumarate in the woodchuck model of chronic HBV infection is both safe and effective[4].
In vivo, Tenofovir hydrate is used for the treatment of HIV-1 infection and chronic hepatitis B. It is administered orally as a prodrug (tenofovir disoproxil fumarate or tenofovir alafenamide) to improve bioavailability. The compound is effective in reducing viral load and improving clinical outcomes in patients with HIV and HBV. Tenofovir hydrate inhibits viral polymerase. In animal models, the compound has been shown to have antiviral activity and is used in studies of viral pathogenesis and drug resistance. The compound's in vivo efficacy and safety profile have been established in clinical trials, and it is now a standard treatment for HIV and HBV. |
| Enzyme Assay |
For reverse transcriptase inhibition assays, the enzymatic activity of recombinant HIV-1 reverse transcriptase is measured using a radiometric or fluorescence-based assay. The enzyme is incubated with varying concentrations of Tenofovir hydrate (0.001-100 µM) in reaction buffer containing 50 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, and 1 mM DTT at 37°C. The reaction is initiated by the addition of a template-primer and [³H]-dATP or fluorescently labeled nucleotides. After incubation, the reaction is terminated, and product formation is measured by scintillation counting or fluorescence. IC50 values are calculated from dose-response curves. For resistance studies, mutant reverse transcriptase enzymes are used to assess the impact of specific mutations on drug susceptibility.
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| Cell Assay |
After plating cells into 48-well tissue culture plates (39,000 cells/mL), they are treated with either vehicle or tenofovir for 48 hours before being removed from the plate. The MTT assay is used to determine cell viability after the treatment period. Tetrazolium dye 3-(4,5-dimethlthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is converted to formazan by NAD(P)H-dependent oxidoreductases, which is how the MTT assay works[1].
For cellular studies, cells (e.g., PBMCs, HK-2 kidney cells) are cultured in appropriate medium (RPMI-1640 or DMEM) with 10% FBS and antibiotics. Cells are seeded in 96-well plates. Tenofovir hydrate is dissolved in DMSO or water and diluted in culture medium to final concentrations (typically 0.1-100 µM). Cells are treated for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. For antiviral assays, HIV- or HBV-infected cells are treated with the compound, and viral replication is measured by p24 antigen ELISA, qPCR, or other methods. Apoptosis is assessed by Annexin V/PI staining or caspase-3/7 activity assays. Oxidative stress markers (ROS, protein carbonylation) are measured using fluorescent probes or colorimetric assays. |
| Animal Protocol |
Twenty adult chronic WHV carrier woodchucks are divided into five treatment groups, each with four animals, based on equal stratification of age, sex, body weight, and serum GGT activity. The five different doses of tenofovir disoproxil fumarate that were administered were as follows: (i) 15.0 mg/kg once a day; (ii) 5.0 mg/kg/day; (iii) 1.5 mg/kg/day; (iv) 0.5 mg/kg/day; and (v) a placebo control. The woodchucks receive daily treatment for four weeks, after which they are monitored for a further twelve weeks[4].
For in vivo efficacy studies, animal models of HIV or HBV infection are used. However, due to the species specificity of HIV, humanized mouse models or other surrogate models are employed. Tenofovir hydrate is formulated in vehicle and administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Viral load is measured in blood and tissues by qPCR. Immune responses and organ toxicity are assessed. For pharmacokinetic studies, blood and tissue samples are collected at various time points for compound quantification by LC-MS. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Tenofovir hydrate indicate that it is a nucleotide analog with low oral bioavailability, which is why it is administered as a prodrug (tenofovir disoproxil fumarate or tenofovir alafenamide). The compound has a plasma half-life that supports once-daily dosing. It is eliminated renally, with a significant proportion excreted unchanged in the urine. The compound's pharmacokinetic properties are well-established from clinical studies. Tenofovir hydrate functions as a stable nucleotide analog, supporting viral polymerase inhibition research.
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| Toxicity/Toxicokinetics |
Toxicological data for Tenofovir hydrate are well-established from clinical use. The compound is generally well-tolerated, but can cause nephrotoxicity, including proximal renal tubulopathy, and decreases in bone mineral density. In vitro, Tenofovir shows cytotoxic effects on HK-2 cells with IC50 values of 9.21 and 2.77 μM at 48 and 72 h. It diminishes ATP levels, increases oxidative stress, and induces apoptosis via mitochondrial damage. The compound is contraindicated in patients with renal impairment. Monitoring of renal function is recommended during treatment.
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| References |
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| Additional Infomation |
Tenofovir hydrate is the monohydrate form of anhydrous tenofovir. It is an antiviral drug and an HIV-1 reverse transcriptase inhibitor. It contains anhydrous tenofovir. Tenofovir is a nucleoside reverse transcriptase inhibitor, an adenosine analogue. It is an adenine analogue reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis B. Because antiviral resistance can occur when used alone, it is usually used in combination with other antiviral drugs to treat HIV infection and chronic hepatitis B. See also: Tenofovir (note moved to).
Tenofovir hydrate (CAS 206184-49-8), also known as GS 1278 or PMPA, is a nucleotide reverse transcriptase inhibitor used for HIV-1 infection and chronic hepatitis B treatment. It has a molecular formula of C₉H₁₆N₅O₅P and a molecular weight of 305.23. The compound blocks reverse transcriptase, a crucial viral enzyme. It is available as a generic medication as of 2017. Tenofovir hydrate is used extensively in antiviral research and is a standard treatment for HIV and HBV. Resistance arises via substitutions in catalytic and nucleotide-binding residues. |
| Molecular Formula |
C9H16N5O5P
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| Molecular Weight |
305.23
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| Exact Mass |
305.089
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| CAS # |
206184-49-8
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| Related CAS # |
Tenofovir;147127-20-6;Tenofovir diphosphate;166403-66-3;Tenofovir maleate;1236287-04-9
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| PubChem CID |
21146529
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| Appearance |
White to off-white solid powder
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| Density |
1.79g/cm3
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| Boiling Point |
616.1ºC at 760mmHg
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| Flash Point |
326.4ºC
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| LogP |
0.465
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
20
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| Complexity |
354
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](CN1C=NC2=C(N=CN=C21)N)OCP(=O)(O)O.O
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| InChi Key |
PINIEAOMWQJGBW-FYZOBXCZSA-N
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| InChi Code |
InChI=1S/C9H14N5O4P.H2O/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14;/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17);1H2/t6-;/m1./s1
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| Chemical Name |
[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid;hydrate
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| Synonyms |
Tenofovir hydrate;tenofovir monohydrate; tenofovir monohydrate; Tenofovir (hydrate); (R)-(((1-(6-Amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonic acid hydrate; 9-[(R)-2-(Phosphonomethoxy)propyl]adenine monohydrate; tenofovir.H2O; Tenofovir [USAN]; GS-1278 hydrate
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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. |
| 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 : ≥ 6 mg/mL (~19.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.6 mg/mL (1.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 6.0 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: ≥ 0.6 mg/mL (1.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 6.0 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: ≥ 0.6 mg/mL (1.97 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 | 3.2762 mL | 16.3811 mL | 32.7622 mL | |
| 5 mM | 0.6552 mL | 3.2762 mL | 6.5524 mL | |
| 10 mM | 0.3276 mL | 1.6381 mL | 3.2762 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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