SM-164

SM-164 is a potent, bivalent, cell-permeable small molecule Smac mimetic that acts as an antagonist of Inhibitor of Apoptosis Proteins (IAPs). It specifically targets X-linked inhibitor of apoptosis protein (XIAP), cellular IAP-1 (cIAP-1), and cellular IAP-2 (cIAP-2) with high affinity. By binding to the BIR2 and BIR3 domains of these proteins, SM-164 induces the rapid degradation of cIAP-1/2 and concurrently antagonizes XIAP, leading to the activation of caspases and induction of TNFα-dependent apoptosis in tumor cells. Preclinical research has demonstrated its efficacy in various malignancies, including triple-negative breast cancer, pancreatic cancer, leukemia, and head and neck squamous cell carcinoma, often showing synergistic effects when combined with other agents like TRAIL.