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Inhibitor of apoptosis (IAP) antagonists target proteins that restrain caspases and cell death signaling. X-linked inhibitor of apoptosis protein (XIAP) was shown in 1997 to inhibit caspases directly through its baculovirus IAP repeat (BIR) domains. The mitochondrial protein second mitochondria-derived activator of caspases (Smac) relieves this block by binding to IAPs. Most listed compounds are Smac mimetics, which cause autoubiquitination and loss of cellular IAP 1 and 2 (cIAP1, cIAP2). This activates nuclear factor kappa B (NF-κB) and cell death driven by tumor necrosis factor alpha (TNF-α). Birinapant, LCL-161, xevinapant and GDC-0152 are examples, and BV-6 acts on cIAP1, cIAP2 and XIAP. Embelin, a natural benzoquinone, is listed as an XIAP inhibitor.