Tenofovir diphosphate is an inhibitor of HIV reverse transcriptase (Kis = 0.022 and 1.55 μM for RNA and DNA, respectively) and hepatitis B virus (HBV) polymerase (Ki = 0.18 μM). It is selective for these enzymes over DNA polymerase α and β, as well as mitochondrial DNA polymerase γ (Kis = 5.2, 81.7, and 59.5 μM, respectively). Tenofovir diphosphate is formed intracellularly through phosphorylation of the prodrugs tenofovir and tenofovir disoproxil by nucleotide kinases. Increased levels of tenofovir diphosphate in isolated peripheral blood mononuclear cells (PBMCs) correlate with a decrease in the risk of simian HIV (SHIV) acquisition in a macaque model of rectal SHIV transmission.
Tenofovir diphosphate (TFV-DP) is a competitive inhibitor of DNA polymerases, specifically targeting dATP, and it serves as a substrate for the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1)[1].
Tenofovir-C3-O-C12-trimethylsilylacetylene (ammonium) displays a prolonged half-life (t1 2) compared to tenofovir in human liver microsomes. Moreover, it demonstrates potent in vitro anti-HIV activity and improves in vivo pharmacokinetic properties.
Tenofovir-C3-O-C15-CF3 (ammonium) demonstrates prolonged half-life values compared to tenofovir in human liver microsomes. It exhibits potent anti-HIV activity in vitro and enhances pharmacokinetic properties in vivo.