Researchers at the University of California, San Diego and Hunter College of the City University of New York (CUNY) have identified potential human molecular targets of the anti-HIV drug Nelfinavir, which may explain why the drug is also effective as a cancer therapy. Their study will be published in the online edition of PLoS Computational Biology on April 28.
Nelfinivir is a protease inhibitor that prevents replication of the HIV virus, but it has also been found to have a positive effect on a number of solid tumor types, and is currently in clinical trial as a cancer therapy. However, the mechanism of how the drug worked in humans was not clear.
The researchers discovered that Nelfinavir may interact with multiple human protein kinases enzymes that modify other proteins and regulate the majority of cellular pathways. Protein kinases comprise approximately 2 percent of the human genome, and are important anti-cancer drug targets.
Surprisingly, the interactions between Nelfinavir and kinases are much weaker than those from more specific, rationally designed drugs, said Philip Bourne, PhD, professor of pharmacology at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. Bourne and colleagues suggest that it is the collective effect of these weak interactions that leads to the clinical efficacy of Nelfinavir.
The research team Li Xie, PhD, from UC San Diego, Thomas Evangelidis, a former graduate student in Bourne's lab, now at the University of Manchester, and research scientist Lei Xie, PhD, now an associate professor at Hunter College, CUNY combined a wide array of computational techniques to investigate the molecular mechanisms underlying Nelfinavir's observed anti-cancer effect.
While drug molecules are designed to bind to targeted proteins in order to achieve a therapeutic effect, small drug molecules can attach to off-target proteins with similar binding sites. The result may
|Contact: Debra Kain|
University of California - San Diego