Tenofovir-d6 (Synonyms: GS-1275-d6, GS-1278-d6, (R)-PMPA-d6, TDF-d6)

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)