Author/Authors :
Philip Jones، نويسنده , , Sergio Altamura، نويسنده , , Prasun K. Chakravarty، نويسنده , , Ottavia Cecchetti، نويسنده , , Raffaele De Francesco، نويسنده , , Paola Gallinari، نويسنده , , Raffaele Ingenito، نويسنده , , Peter T. Meinke، نويسنده , , Alessia Petrocchi، نويسنده , , Michael Rowley، نويسنده , , Rita Scarpelli، نويسنده , , Sergio Serafini، نويسنده , , Christian Steinkühler، نويسنده ,
Abstract :
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.
