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Similar to Smac/DIABLO, HtrA2/Omi binds to and neutralizes IAPs (XIAP, cIAP1, and cIAP2) via its N-terminal IAP-binding motif, therefore releasing the inhibition of IAP to caspase-3, -7, and -9.
Our results of weak expression of AIF and HtrA2/Omi in SLL/CLL, combined with previous studies of total lack of Smac/DIABLO expression (9) and variable expression of cIAP1 and cIAP2 in SLL/CLL, (21) appear to support the notion that this lymphoma is characterized by defective apoptosis.
AT-406 is a multi-IAP inhibitor (including XIAP, cIAP1, cIAP2, ML-IAP).