Tenofovir diphosphate

Tenofovir diphosphate is an inhibitor of HIV reverse transcriptase (K_is = 0.022 and 1.55 ?M for RNA and DNA, respectively) and hepatitis B virus (HBV) polymerase (K_i = 0.18 ?M).^1,2 It is selective for these enzymes over DNA polymerase α and β, as well as mitochondrial DNA polymerase γ (K_is = 5.2, 81.7, and 59.5 ?M, respectively). Tenofovir diphosphate is formed intracellularly through phosphorylation of the prodrugs tenofovir and tenofovir disoproxil by nucleotide kinases.³ 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.⁴

1.Cherrington, J.M., Allen, S.J.W., Bischofberger, N., et al.Kinetic interaction of the diphosphates of 9-(2-phosphonylmethoxyethyl)adenine and other anti-HIV active purine congeners with HIV reverse transcriptase and human DNA polymerases α, β and γAntivir. Chem. Chemother.6(4)217-221(1995) 2.Delaney, W.E., IV, Ray, A.S., Yang, H., et al.Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virusAntimicrob. Agents Chemother.50(7)2471-2477(2006) 3.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)PMPAAntimicrob. Agents Chemother.42(3)612-617(1998) 4.Anderson, P.L., Glidden, D.V., Bushman, L.R., et al.Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmissionJ. Antimicrob. Chemother.69(9)2470-2476(2014)