Nelfinavir (
Viracept) was originally designed as a specific
HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV
drug. Although
nelfinavir is being increasingly displaced by second generation
HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect:
nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in
cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in
cancer cells by the so-called endoplasmic reticulum/unfolded
protein stress response, allowing
nelfinavir to act on otherwise chemo-resistant
cancer cells. Furthermore, anti-microbial effects of
nelfinavir have been described, including an efficacy against
malaria,
tuberculosis, and SARS. Several
cancer-related clinical studies on
nelfinavir as a single agent or in combination
therapies have been launched and are expected to add to the usefulness of this versatile
drug for
cancer treatment strategies or other purposes.