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Jones, Philip; Altamura, Sergio; Chakravarty, Prasun K.; Cecchetti, Ottavia; Francesco, Raffaele De; Gallinari, Paola; Ingenito, Raffaele; Meinke, Peter T.; Petrocchi, Alessia; Rowley, Michael; Scarpelli, Rita; Serafini, Sergio; Steinkühler, Christian
Bioorganic & medicinal chemistry letters, 12/2006, Letnik: 16, Številka: 23Journal Article
The evolution of a novel series of HDAC inhibitors containing an unusual ketone zinc binding group is described. SAR studies resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors. Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid ( L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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