BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Proteasome

March 26, 2015 7:00 AM UTC

In vitro and mouse studies suggest a novel proteasome inhibitor could help treat cancer. Virtual and chemical screening of a small molecule library and subsequent chemical optimization of hits identified a lead pyrazole-based proteasome inhibitor that induced apoptosis in multiple human cancer cells, including lines with acquired resistance to the protease inhibitors bortezomib or carfilzomib, at IC50 values of about 1.0 μM. In a mouse xenograft model of prostate cancer, the inhibitor decreased tumor growth compared with vehicle without causing weight loss or other overt toxicities. Next steps could include additional in vivo efficacy and safety studies of the inhibitor...