(S)-MG115 is a potent and reversible proteasome inhibitor, targeting the chymotryptic site on the 20S particle (Ki = 21 nM). It reduces the degradation of ubiquitin-conjugated proteins in extracts. (S)-MG115 also blocks the degradation of long- and short-lived proteins in intact cells as well as the proteolytic generation of diverse proteins, including NF-κB, antigens, and p53. Proteasome inhibitors, including (S)-MG115, can induce a heat shock response and apoptosis, particularly in cancer cells.