Title:Towards Isozyme-Selective HDAC Inhibitors For Interrogating Disease
Volume: 12
Issue: 14
Author(s): Praveer Gupta, Robert C. Reid, Abishek Iyer, Matthew J. Sweet and David P. Fairlie
Affiliation:
Keywords:
Histone deacetylase, HDAC inhibitor, isoform, isozyme, cancer, inflammation, metabolic, promising targets, immunological, cardiovascular, cytotoxic, lysine residues, cellular proteins, phosphorylation, small molecule chemical inhibitors, therapeutic drugs
Abstract: Histone deacetylase (HDAC) enzymes have emerged as promising targets for the treatment of a wide range of
human diseases, including cancers, inflammatory and metabolic disorders, immunological, cardiovascular, and infectious
diseases. At present, such applications are limited by the lack of selective inhibitors available for each of the eighteen
HDAC enzymes, with most currently available HDAC inhibitors having broad-spectrum activity against multiple HDAC
enzymes. Such broad-spectrum activity maybe useful in treating some diseases like cancers, but can be detrimental due to
cytotoxic side effects that accompany prolonged treatment of chronic diseased states. Here we summarize progress towards
the design and discovery of HDAC inhibitors that are selective for some of the eleven zinc-containing classical
HDAC enzymes, and identify opportunities to use such isozyme-selective inhibitors as chemical probes for interrogating
the biological roles of individual HDAC enzymes in diseases.
