XIAP, cIAP1, cIAP2

X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein 1 (cIAP1), and cellular inhibitor of apoptosis protein 2 (cIAP2) are members of the inhibitor of apoptosis protein family, defined by the presence of BIR (baculoviral IAP repeat) domains and often a C-terminal RING domain conferring E3 ubiquitin ligase activity[7]. XIAP primarily inhibits apoptosis by directly binding and inhibiting caspases-3, -7, and -9, while cIAP1 and cIAP2 regulate cell death pathways indirectly through ubiquitination of signaling molecules in the TNF receptor pathway and the regulation of NF-κB signaling[2][5][7]. These proteins are overexpressed in various cancers and contribute to tumor cell survival and resistance to chemotherapy, making them important therapeutic targets. Drugs targeting these proteins, especially Smac mimetics, are in advanced clinical development for cancer therapy[2][4][6].

Other names

BIRC4X-linked IAPBIRC2BIRC3IAPsinhibitor of apoptosis proteins

Drugs bind to the BIR domains of IAPs, disrupting their ability to inhibit caspases, leading to increased apoptosis in cancer cells; Many Smac mimetics induce autoubiquitination and subsequent proteasomal degradation of cIAP1 and cIAP2, sensitizing cells to TNFα-induced apoptosis