New prospects for nelfinavir in non-HIV-related diseases.
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.
Brüning
Ansgar
A
Ludwig-Maximilians University Munich, Department of Obstetrics/Gynecology, Campus Innenstadt, Munich, Germany. ansgar.bruening@med.uni-muenchen.de
Gingelmaier
Andrea
A
Friese
Klaus
K
Mylonas
Ioannis
I
D019380:Anti-HIV Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D006801:Humans; D019888:Nelfinavir / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D019888:Nelfinavir