SM-122

SM-122 is a monovalent small-molecule Smac (Second Mitochondrial-derived Activator of Caspases) mimetic developed as a targeted anticancer agent. It functions by binding to the BIR (Baculoviral IAP Repeat) domains of Inhibitor of Apoptosis Proteins (IAPs), specifically targeting cellular IAP-1 (cIAP-1) and cellular IAP-2 (cIAP-2) for rapid proteasomal degradation. This degradation leads to the stabilization of NIK and the activation of the non-canonical NF-κB pathway, ultimately inducing tumor necrosis factor-alpha (TNFα)-dependent apoptosis in sensitive tumor cells. While SM-122 effectively antagonizes cIAPs, it is significantly less potent than bivalent Smac mimetics, such as SM-164, in its ability to bind and inhibit X-linked IAP (XIAP). SM-122 is primarily used in preclinical research to study IAP biology and the therapeutic potential of IAP antagonism.