Cyclopeptide Smac mimetics as antagonists of IAP proteins

Two cyclopeptidic Smac mimetics, 2 and 3, were designed and synthesized. These two compounds bind to XIAP and cIAP-1/2 with low nanomolar affinities, and restore the activities of caspase-9 and caspase-3/-7 inhibited by XIAP. Compound 2 potently inhibits cancer cell growth and is 5–8 times more potent than the initial lead compound.

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