Identification of a potent non-hydroxamate histone deacetylase inhibitor by mechanism-based drug design

In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, we synthesized several suberoylanilide hydroxamic acid (SAHA)-based compounds designed on the basis of the catalytic mechanism of HDACs. Among these compounds, mercaptoacetamide 5b was found to be as potent as SAHA. Kinetic enzyme assays and molecular modeling are also reported.