MG-115 (CAS 133407-86-0)

MG-115 is a potent and reversible inhibitor of the proteasome, specifically targeting the chymotrypsin-like activity of this cellular complex. By inhibiting both the 20S and 26S proteasomes, MG-115 has demonstrated the ability to induce apoptosis in Rat-1 and PC12 cells through a p53-dependent pathway. Notably, MG-115′s inhibition of the ubiquitin-proteasome system (UPS) triggers the activation of autophagy, an interconnected protein degradation system. With a Ki value of 21 nM, MG-115 effectively blocks the chymotryptic site on the 20S particle, resulting in reduced degradation of ubiquitin-conjugated proteins in cell extracts. In intact cells, it also hinders the degradation of both short-lived and long-lived proteins and prevents the proteolytic generation of various proteins, including NF-κB, antigens, and p53. In cancer cells, proteasome inhibitors such as MG-115 have been known to elicit a heat shock response and induce apoptosis. Overall, MG-115 is a compound that exerts its inhibitory effects on the proteasome, primarily targeting its chymotrypsin-like activity.