Procaspase-3 is an inactive form of caspase-3 (a cysteine protease involved in apoptosis) and the “conversion of procaspase-3 to caspase-3 results in the generation of the active ‘executioner’ caspase that subsequently catalyzes the hydrolysis of many protein substrates.” Putt et al. screened a library of 20,500 compounds and identified a small-molecule – named PAC-1 – that activated procaspase-3 in vitro. They then showed that the small-molecule could induce apoptosis in a variety of cancer cell lines. Since PAC-1 was orally active in live mice and was able to retard tumor growth in three cancer models, the authors believe that this molecule (or its derivatives) could be used to treat cancer in humans one day.
If you want to learn more about the work and you’re attending the fall ACS meeting, Karson Putt will be talking about the work on Tuesday, September 12th in the Medicinal Chemistry Award Symposium. Paul Hergenrother will also be talking in that session (and receiving the award), though he will focus on new small-molecules that might be able to combat Parkinson’s Disease.
Joshua Finkelstein (Associate Editor, Nature)