Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors

The development of selective histone deacetylase inhibitors (HDACi) and thus the identification of suitable chemical probes is still highly complex. Moreover, in the past, the results of oversimplified biochemical HDAC assays have often been overinterpreted. This has led to the extensive use of various supposedly isoform-selective HDACi as chemical probes to investigate the biological function of specific HDAC isoforms and classes. Considering more recent insights concerning the structure, binding kinetics, as well as substrate specificity of several HDAC isoforms, at least some of these studies should be reevaluated thoroughly. In this review, we present a selection of possible tool compounds for use in biological and pharmacological studies to investigate the biological function of specific HDAC isoforms or classes and comprehensively discuss their limitations based on the currently available data.