Parthenolide is a naturally occurring compound that has long been used in traditional medicine. It has anti-inflammatory, antimicrobial and anti-cancer properties. Its anti-cancer effects are based on its ability to interfere with several cellular signalling pathways. The most well-characterised of these are the inhibition of the NF-κB pathway and STAT proteins, and the induction of oxidative stress. Parthenolide also induces severe mitotic arrest; however, the exact mechanism underlying this phenomenon is not well understood. Collaborative research between the Danish Cancer Institute and the University of Copenhagen, combining cell biology and click chemistry, identified the BugZ protein as a parthenolide target that mediates mitotic arrest (manuscript under review).

In this HALRIC project, we propose using X-ray crystallography and HDX-MS at the University of Oslo to characterise the parthenolide-BugZ complex, as well as using click chemistry and in silico chemical engineering to produce parthenolide derivatives with improved potency, which will then be tested in cell experiments at the University of Copenhagen. This research will reveal how parthenolide works and identify promising candidates for developing more effective, targeted cancer therapies.