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Online ISSN: 1860-7187
June 27, 2010
VIP: Synthesis and Biological Characterization of Amidopropenyl Hydroxamates as HDAC Inhibitors
Florian Thaler,* Mario Varasi, Andrea Colombo, Roberto Boggio, Davide Munari, Nickolas Regalia, Marco G. Rozio, Veronica Reali, Anna E. Resconi, Antonello Mai, Stefania Gagliardi, Giulio Dondio, Saverio Minucci, and Ciro Mercurio
A series of highly potent histone deacetylase (HDAC) inhibitors has been developed by a team of researchers from academic, industry, and government settings. Because aberrant HDAC activity has been linked to several diseases including cancer, compounds that effect its specific blockade are heavily sought after. In an effort to improve the potency and pharmacokinetic (PK) profile of compounds that block HDAC activity, Thaler et al. used a novel amidopropenyl hydroxamic acid scaffold in their syntheses. Biological characterization showed that several of the resulting compounds show good in vitro potency and remarkably high microsomal stability. Their work also indicates that these compounds are catabolized by non-microsomal enzymes, as relatively high clearance rates were observed in in vivo PK studies.
Received April 19, 2010; published online June 22, 2010, DOI: 10.1002/cmdc.201000166.