Tenofovir

Names

[ Name ]:
Tenofovir

[Synonym ]:
(R)-(((1-(6-Amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonic acid
(R)-(1-(6-amino-9H-purin-9-yl)propan-2-yloxy)methylphosphonic acid
D,L-TENOFOVIR
Apropovir
9-Pmpa
MFCD07357269
Tenefovir
GS-1278
1-(6-Aminopurin-9-yl)propan-2-yloxymethylphosphonic acid

Biological Activity

[Description]:

Tenofovir is a nucleotide reverse transcriptase inhibitor to treat HIV and chronic Hepatitis B.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> HIV

Signaling Pathways >> Anti-infection >> Reverse Transcriptase

Research Areas >> Infection

[In Vitro]

Tenofovir 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. Tenofovir (3.0 to 28.8 μM) increases oxidative stress and protein carbonylation in HK-2 cells. Furthermore, Tenofovir induces apoptosis in HK-2 cells, and that apoptosis is induced via mitochondrial damage[1]. Tenofovir and M48U1 formulated in 0.25% HEC each 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 combined formulation of M48U1 and tenofovir in 0.25% HEC exhibits synergistic antiretroviral activity against infection with R5-tropic HIV-1BaL, and is not toxic to PBMCs[2].

[In Vivo]

Tenofovir Disoproxil Fumarate (20, 50, 140, or 300 mg/kg) administered to BLT mice, shows dose dependent activity during vaginal HIV challenge in BLT humanized mice. Tenofovir Disoproxil Fumarate (50, 140, 300 mg/kg) significantly reduces HIV transmission in BLT mice[3]. Tenofovir Disoproxil Fumarate (0.5, 1.5, or 5.0 mg/kg/day, p.o.) induces a dose-dependent decline in serum viremia in woodchucks chronically infected with WHV. Tenofovir Disoproxil Fumarate administration is safe and effective in the woodchuck model of chronic HBV infection[4].

[Cell Assay]

Cells are plated into 48-well tissue culture plates (39,000 cells/mL) and allowed to grow for 48 h followed by treatment with vehicle or Tenofovir. Following the treatment period, cell viability is assessed using the MTT assay. The MTT assay relies on the conversion of tetrazolium dye 3-(4,5-dimethlthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan by NAD(P)H-dependent oxidoreductases[1].

[Animal admin]

Twenty adult chronic WHV carrier woodchucks are stratified equally by age, sex, body weight, and serum GGT activity into five treatment groups consisting of four animals each: (i) Tenofovir Disoproxil Fumarate at 15.0 mg/kg once per day, (ii) Tenofovir Disoproxil Fumarate at 5.0 mg/kg/day, (iii) Tenofovir Disoproxil Fumarate at 1.5 mg/kg/day, (iv) Tenofovir Disoproxil Fumarate at 0.5 mg/kg/day, and (v) a placebo control. The woodchucks are treated daily for 4 weeks and observed for an additional 12 weeks following cessation of drug treatment[4].

[References]

[1]. Murphy RA, et al. Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity. Int J Mol Sci. 2017 Mar 1;18(3).

[2]. Musumeci G, et al. M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures. Sci Rep. 2017 Feb 1;7:41018.

[3]. Wahl A, et al. 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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.8±0.1 g/cm3

[ Boiling Point ]:
616.1±65.0 °C at 760 mmHg

[ Melting Point ]:
276-280°C

[ Molecular Formula ]:
C₉H₁₄N₅O₄P

[ Molecular Weight ]:
287.212

[ Flash Point ]:
326.4±34.3 °C

[ Exact Mass ]:
287.078339

[ PSA ]:
146.19000

[ LogP ]:
-1.71

[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C

[ Index of Refraction ]:
1.740

[ Storage condition ]:
Store at -20°C

[ Water Solubility ]:
13.4 mg/mL (25 ºC)

Safety Information

[ Hazard Codes ]:
C

[ Risk Phrases ]:
R34:Causes burns.

[ Safety Phrases ]:
S22-S26-S27-S36/37/39-S45

[ RIDADR ]:
UN 3261 8/PG 2

[ WGK Germany ]:
3

[ RTECS ]:
DB8930000

[ Packaging Group ]:
III

[ Hazard Class ]:
8

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%