Novel cancer-starving target identified

Antiangiogenesis agents, which are drugs that inhibit blood vessel growth in an effort to starve tumors, are hot medicinal commodities, with several compounds in clinical trials or already approved. In an effort to find new angiogenesis inhibitors, Jun O. Liu of Johns Hopkins University School of Medicine and coworkers screened a library of drugs approved previously by FDA and other drug agencies (ACS Chem. Biol., DOI: 10.1021/cb600362d).

The screen yielded several drugs that inhibit endothelial cell proliferation, which is required for angiogenesis. One of the most promising and unexpected hits was itraconazole (Sporanox, shown), a Janssen Pharmaceutica drug used to treat fungal infections of the skin and nails. The molecular mechanism of itraconazole's antiangiogenic activity turns out to involve inhibition of the enzyme lanosterol 14α-demethylase. Liu and coworkers verified that this enzyme is essential for endothelial cell proliferation and angiogenesis, which was not previously known, thereby making it an intriguing target for the discovery of other new angiogenesis inhibitors, they note.