Pyridylalanine-Containing Hydroxamic Acids as Selective HDAC6 Inhibitors (pages 283–290)
Stefan Schäfer, Laura Saunders, Sonja Schlimme, Vassil Valkov, Julia M. Wagner, Felix Kratz, Wolfgang Sippl, Eric Verdin and Manfred Jung
Article first published online: 17 DEC 2008 | DOI: 10.1002/cmdc.200800196
Pyridylalanine inhibitors of histone deacetylase (HDAC) have been synthesized that show selectivity for the isoform HDAC6 over HDAC1 in vitro. This selectivity was also identified in cancer cells by analyzing tubulin versus histone acetylation. The compounds show decreased intrinsic cytotoxicity relative to pan-HDAC inhibitors, but show antiproliferative synergy with the proteasome inhibitor bortezomib.