Tenofovir-d6 is intended for use as an internal standard for the quantification of tenofovir by GC- or LC-MS. Tenofovir is an analog of adenosine monophosphate that has antiviral activity.1,2 It is converted by cellular enzymes to tenofovir diphosphate, an obligate chain terminator that inhibits the activity of HIV reverse transcriptase and hepatitis B virus polymerase.3,4 Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α and β and mitochondrial DNA polymerase γ.4 For in vivo and cell culture use, tenofovir is supplied as a water soluble prodrug in the form of tenofovir disoproxil (fumarate) , which increases the intracellular diphosphorylated compound >1,000-fold above the level attained with unmodified tenofovir.
1.Balzarini, J., Vahlenkamp, T., Egberink, H., et al.Antiretroviral activities of acyclic nucleoside phosphonates [9-(2-phosphonylmethoxyethyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, (R)-9-(2-phosphonylmethoxypropyl)adenine, and MDL 74,968] in cell cultures and murine sarcoma virus-infected newborn NMRI miceAntimicrobial Agents and Chemotherapy41(3)611-616(1997) 2.Balzarini, J., Holy, A., Jindrich, J., et al.Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: Potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurineAntimicrobial Agents and Chemotherapy37(2)332-338(1993) 3.Van Gelder, J., Shafiee, M., De Clercq, E., et al.Species-dependent and site-specific intestinal metabolism of ester prodrugsInternational Journal of Pharmacy205(1-2)93-100(2000) 4.Robbins, B.L., Srinivas, R.V., Kim, C., et al.Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2-phosphonomethoxypropyl)adenine (PMPA), bis(isopropyloxymethylcarbonyl)PMPAAntimicrobial Agents and Chemotherapy42(3)612-617(1998)