| Literature DB >> 23062821 |
Daniele Lecis1, Eloise Mastrangelo, Laura Belvisi, Martino Bolognesi, Monica Civera, Federica Cossu, Michelandrea De Cesare, Domenico Delia, Carmelo Drago, Giacomo Manenti, Leonardo Manzoni, Mario Milani, Elisabetta Moroni, Paola Perego, Donatella Potenza, Vincenzo Rizzo, Cinzia Scavullo, Carlo Scolastico, Federica Servida, Francesca Vasile, Pierfausto Seneci.
Abstract
Novel pro-apoptotic, homodimeric and heterodimeric Smac mimetics/IAPs inhibitors connected through head-head (8), tail-tail (9) or head-tail linkers (10), were biologically and structurally characterized. In vitro characterization (binding to BIR3 and linker-BIR2-BIR3 domains from XIAP and cIAP1, cytotoxicity assays) identified early leads from each dimer family. Computational models and structural studies (crystallography, NMR, gel filtration) partially rationalized the observed properties for each dimer class. Tail-tail dimer 9a was shown to be active in a breast and in an ovary tumor model, highlighting the potential of dimeric Smac mimetics/IAP inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold as potential antineoplastic agents.Entities:
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Year: 2012 PMID： 23062821 DOI： 10.1016/j.bmc.2012.09.041
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641