Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors 
show promise as therapeutics for the neurodegenerative diseases Friedreich's 
ataxia (FRDA) and Huntington's disease (HD). While it is clear that HDAC3 is one 
of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of 
other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial 
effects of these compounds in FRDA and HD, and other HDAC interacting proteins 
may be impacted by the compound. To this end, we synthesized activity-based 
profiling probe (ABPP) versions of one of our HDAC inhibitors (compound 106), 
and in the present study we used a quantitative proteomic method coupled with 
multidimensional protein identification technology (MudPIT) to identify the 
proteins captured by the ABPP 106 probe. Nuclear proteins were extracted from 
FRDA patient iPSC-derived neural stem cells, and then were reacted with control 
and ABPP 106 probe. After reaction, the bound proteins were digested on the 
beads, and the peptides were modified using stable isotope-labeled formaldehyde 
to form dimethyl amine. The selectively bound proteins determined by mass 
spectrometry were subjected to functional and pathway analysis. Our findings 
suggest that the targets of compound 106 are involved not only in 
transcriptional regulation but also in posttranscriptional processing of mRNA.