ABSTRACT
Histones are the major structural proteins around which more than 2 m of DNA in every eukaryotic cell is organized. A number of different histone deacetylase (HDAC) inhibitors have made their way into the clinic. The involvement of the histone acetyltransferases and HDACs in cancer is well established. The HDAC family comprises three distinct classes of enzymes, classes I, II, and III. The history of HDAC inhibitors began in 1970s when several reports, including a sentinel observation from Riggs et al., noted that butyric acid can stop DNA synthesis and cell proliferation and induce histone acetylation and differentiation in erythroleukemic cells. HDAC inhibitors target numerous other protein substrates besides histones. One important target includes Bcl-6, one of the most commonly altered genes in diffuse large B-cell lymphoma. suberolyanilide hydroxamic acid, vorinostat, is the prototypical hyroxamate that has to date been extensively studied in the clinic and recently approved by the FDA for the treatment of cutaneous T-cell lymphoma.
