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Tenofovir hydrate (formerly also known as GS-1278; PMPA; TDF) is an approved anti-HIV drug that blocks reverse transcriptase and hepatitis B virus infections. Tenofovir is an antiretroviral medication used to prevent and treat HIV/AIDS and to treat chronic hepatitis B. Tenofovir reduces the viral cytopathic effect of HIV-1(IIIB), HIV-2(ROD) and HIV(EHO) with EC50 of 1.15 μg/mL, 1.12 μg/mL and 1.05 μg/mL in MT-4 cells. Tenofovir also reduces the viral cytopathic effect of SIV(mac251) , SIV(B670) ,SHIV(89.6) and SHIV(RTSHIV). Tenofovir is the active substance of tenofovir disoproxil which is a prodrug that is used because of its better absorption in the gut.
Physicochemical Properties
| Molecular Formula | C9H16N5O5P |
| Molecular Weight | 305.23 |
| Exact Mass | 305.089 |
| CAS # | 206184-49-8 |
| Related CAS # | Tenofovir;147127-20-6;Tenofovir diphosphate;166403-66-3;Tenofovir maleate;1236287-04-9 |
| PubChem CID | 21146529 |
| Appearance | White to off-white solid powder |
| Density | 1.79g/cm3 |
| Boiling Point | 616.1ºC at 760mmHg |
| Flash Point | 326.4ºC |
| LogP | 0.465 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 20 |
| Complexity | 354 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C[C@H](CN1C=NC2=C(N=CN=C21)N)OCP(=O)(O)O.O |
| InChi Key | PINIEAOMWQJGBW-FYZOBXCZSA-N |
| 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 |
| Chemical Name | [(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid;hydrate |
| 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 |
| 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 (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) |
Biological Activity
| Targets | HIV-1/2 nucleotide reverse transcriptase |
| 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]. |
| 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]. |
| 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]. |
| 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]. |
| References |
[1]. Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity. Int J Mol Sci. 2017 Mar 1;18(3):531. [2]. M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures. Sci Rep. 2017 Feb 1;7:41018. [3]. Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic-Pharmacodynamic In Vivo Model. Sci Rep. 2017 Feb 1;7:41098. [4]. Menne S, Cote PJ, Korba BE, Antiviral effect of oral administration of tenofovir disoproxil fumarate in woodchucks with chronic woodchuck hepatitis virus infection. Antimicrob Agents Chemother. 2005 Jul;49(7):2720-8. |
| Additional Infomation |
Tenofovir hydrate is a hydrate that is the monohydrate form of anhydrous tenovir. It has a role as an antiviral drug and a HIV-1 reverse transcriptase inhibitor. It contains a tenofovir (anhydrous). Tenofovir is a nucleoside reverse transcriptase inhibitor analog of adenosine. An adenine analog REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B. It is used to treat HIV INFECTIONS and CHRONIC HEPATITIS B, in combination with other ANTIVIRAL AGENTS, due to the emergence of ANTIVIRAL DRUG RESISTANCE when it is used alone. See also: Tenofovir (annotation moved to). |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 6 mg/mL (~19.66 mM) |
| 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. 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. 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 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 | 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 |