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ID: ALA2401611
Journal: Bioorg Med Chem Lett
Title: Design, synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP.
Authors: Ardecky RJ, Welsh K, Finlay D, Lee PS, González-López M, Ganji SR, Ravanan P, Mace PD, Riedl SJ, Vuori K, Reed JC, Cosford ND.
Abstract: We recently reported the systematic ligand-based rational design and synthesis of monovalent Smac mimetics that bind preferentially to the BIR2 domain of the anti-apoptotic protein XIAP. Expanded structure-activity relationship (SAR) studies around these peptidomimetics led to compounds with significantly improved selectivity (>60-fold) for the BIR2 domain versus the BIR3 domain of XIAP. The potent and highly selective IAP antagonist 8q (ML183) sensitized TRAIL-resistant prostate cancer cells to apoptotic cell death, highlighting the merit of this probe compound as a valuable tool to investigate the biology of XIAP.
CiteXplore: 23743278