Tenofovir Diphosphate Is a Poor Substrate and a Weak Inhibitor of Rat DNA Polymerases α, δ, and ɛ*

Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) α, δ, and ɛ*, with values for the K(i) for PMPApp ((PMPApp)K(i)) relative to the K(m) for dATP ((dATP)K(m)) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)K(m) values 350-, 2,155-, and 187-fold higher than (dATP)K(m) values for pol α, δ, and ɛ*, respectively.