(S)-Tenofovir [known also as (S)-GS 1278], the S-enantiomer of Tenofovir and a less active isomer, is a nucleotide reverse transcriptase inhibitor to treat HIV and chronic Hepatitis B (HBV). Tenofovir (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	C9H14N5O4P
Molecular Weight	287.21
Exact Mass	287.078
Elemental Analysis	C, 37.64; H, 4.91; N, 24.38; O, 22.28; P, 10.78
CAS #	147127-19-3
Related CAS #	Tenofovir diphosphate;166403-66-3; Tenofovir Disoproxil fumarate;202138-50-9;Tenofovir hydrate;206184-49-8;Tenofovir diphosphate;166403-66-3;Tenofovir maleate;1236287-04-9
PubChem CID	122767
Appearance	Typically exists as White to off-white solids at room temperature
Density	1.79g/cm3
Boiling Point	616.1ºC at 760mmHg
Flash Point	326.4ºC
Vapour Pressure	4.92E-16mmHg at 25°C
Index of Refraction	1.739
LogP	0.53
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	19
Complexity	354
Defined Atom Stereocenter Count	1
SMILES	P(C([H])([H])O[C@@]([H])(C([H])([H])[H])C([H])([H])N1C([H])=NC2=C(N([H])[H])N=C([H])N=C12)(=O)(O[H])O[H]
InChi Key	SGOIRFVFHAKUTI-LURJTMIESA-N
InChi Code	InChI=1S/C9H14N5O4P/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)/t6-/m0/s1
Chemical Name	[(2S)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid
Synonyms	(S)-GS 1278; (S)-PMPA; (S)-(((1-(6-Amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonic acid; (S)-Tenofovir; (S)-PMPA; [(2S)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid; ({[(2S)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid; (S)-9-(2-Phosphonylmethoxypropyl)adenine; Phosphonic acid, P-[[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-; (S)-TDF
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
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	HBV; nucleotide reverse transcriptase
ln Vitro	Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2). HK-2 cells were grown for 48 h followed by 24 to 72 h exposure to 0-28.8 μM TFV or vehicle, phosphate buffered saline (PBS). MTT (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Trypan blue indicated that TFV diminished cell viability at 24-72 h. TFV decreased ATP levels at 72 h when compared to vehicle, reflecting mitochondrial dysfunction. TFV increased the oxidative stress biomarkers of protein carbonylation and 4-hydroxynonenol (4-HNE) adduct formation. Tumor necrosis factor alpha (TNFα) was released into the media following exposure to 14.5 and 28.8 μM TFV. Caspase 3 and 9 cleavage was induced by TFV compared to vehicle at 72 h. These studies show that HK-2 cells are a sensitive model for TFV cytotoxicity and suggest that mitochondrial stress and apoptosis occur in HK-2 cells treated with TFV[1].
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).

Solubility Data

Solubility (In Vitro)

DMSO : ~5 mg/mL (~17.41 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.5 mg/mL (1.74 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 5.0 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: ≥ 0.5 mg/mL (1.74 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 5.0 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: ≥ 0.5 mg/mL (1.74 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 5.0 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	3.4818 mL	17.4089 mL	34.8177 mL
	5 mM	0.6964 mL	3.4818 mL	6.9635 mL
	10 mM	0.3482 mL	1.7409 mL	3.4818 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.