X-linked inhibitor of apoptosis protein (XIAP) is a member of the family of inhibitor of apoptosis proteins and part of the programmed cell death (apoptosis) pathway. Also known as BIRC4 (baculovirus IAP repeat-containing 4), XIAP resides in the cytoplasm. It acts as an inhibitor of caspases by directly binding to and inhibiting caspases 3, 7, and 9 and thus may inhibit both the intrinsic and extrinsic apoptosis pathways. Protein and RNA levels of XIAP can be measured but there are currently no FDA-approved tests for the measurement of XIAP in either tumor tissue or blood. XIAP is overexpressed in numerous malignancies. XIAP is currently being investigated as a predictive and prognostic tool in cancer and as a marker of resistance to cancer therapies. Restoration of apoptosis is an important priority for cancer drug development, thus targeting of XIAP is of critical significance. Second mitochondrial-derived activator of caspases (SMAC)-mimetics such as LCL-161 and antisense oligonucleotides such as AEG35156 inhibit XIAP and are being investigated in therapeutic clinical trials.
KeywordsAT-406 Baculovirus IAP repeat-containing 4 (BIRC4). See X-linked inhibitor of apoptosis protein (XIAP) Birinapant HGS-1029 LCL-161 Smac mimetics X-linked inhibitor of apoptosis protein (XIAP) AEG35156 Assessment Chemoresistance Diagnostic marker Immunohistochemistry In cancer Preclinical studies Response to chemotherapy Smac mimetics Therapeutics XLP2 Zinc-binding domain X-linked lymphoproliferative disease 2 (XLP2)
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