Hexadecyloxypropyl-cidofovir (
HDP-CDV) is a novel
ether lipid conjugate of (S)-1-(3-hydroxy-2-phosphonoylmethoxypropyl)-cytosine (CDV) which exhibits a remarkable increase in
antiviral activity against orthopoxviruses compared with CDV. In contrast to CDV,
HDP-CDV is orally active and lacks the nephrotoxicity of CDV itself. Increased oral bioavailability and increased cellular uptake is facilitated by the
lipid portion of the molecule which is responsible for the improved activity profile. The
lipid portion of
HDP-CDV is cleaved in the cell, releasing CDV which is converted to CDV
diphosphate, the active metabolite.
HDP-CDV is a highly effective agent against a variety of
orthopoxvirus infections in animal models of disease including
vaccinia,
cowpox, rabbitpox and
ectromelia. Its activity was recently demonstrated in a case of human disseminated
vaccinia infection after it was added to a multiple
drug regimen. In addition to the activity against orthopoxviruses,
HDP-CDV (
CMX001) is active against all
double stranded DNA viruses including CMV, HSV-1, HSV-2, EBV, adenovirus, BK virus, orf, JC, and
papilloma viruses, and is under clinical evaluation as a treatment for human
infections with these agents.