LCL161 is a small-molecule SMAC mimetic structurally designed to reproduce the N-terminal AVPI binding motif of endogenous SMAC. This peptidomimetic scaffold allows high-affinity binding to the baculoviral IAP repeat domains of inhibitor of apoptosis proteins such as cIAP1 and cIAP2. By antagonizing these proteins, LCL161 disrupts their interaction with caspases, enabling caspase activation and TNFα-mediated cell death. This mechanism sensitizes cancer cells to OV–induced apoptosis and amplifies immunogenic cell death, enhancing viral oncolysis and immune clearance. Here, TNF is linked to cancer.