Serendipity in discovery of proteasome inhibitors.

Abstract Among its various catalytic activities, the ‘chymotrypsin-like’ activity of the proteasome, a large multicatalytic proteinase complex has emerged as the focus of drug discovery efforts in cancer therapy. Herein, a series of first generation (2 S , 3 R )-2-amino-3-hydroxybutyric acid derived proteasome inhibitors that were discovered serendipitously en route to original goal of generating a series of sterically constrained oxazoline derivatives has been reported.