VORINOSTAT INHIBITS THE ENZYMATIC ACTIVITY OF HISTONE DEACETYLASES HDAC1, HDAC2 AND HDAC3 (CLASS I) AND HDAC6 (CLASS II) AT NANOMOLAR CONCENTRATIONS (IC50 < 86 NM). THESE ENZYMES CATALYZE THE REMOVAL OF ACETYL GROUPS FROM THE LYSINE RESIDUES OF PROTEINS, INCLUDING HISTONES AND TRANSCRIPTION FACTORS. IN SOME CANCER CELLS, THERE IS AN OVEREXPRESSION OF HDACS, OR AN ABERRANT RECRUITMENT OF HDACS TO ONCOGENIC TRANSCRIPTION FACTORS CAUSING HYPOACETYLATION OF CORE NUCLEOSOMAL HISTONES. HYPOACETYLATION OF HISTONES IS ASSOCIATED WITH A CONDENSED CHROMATIN STRUCTURE AND REPRESSION OF GENE TRANSCRIPTION. INHIBITION OF HDAC ACTIVITY ALLOWS FOR THE ACCUMULATION OF ACETYL GROUPS ON THE HISTONE LYSINE RESIDUES RESULTING IN AN OPEN CHROMATIN STRUCTURE AND TRANSCRIPTIONAL ACTIVATION. IN VITRO, VORINOSTAT CAUSES THE ACCUMULATION OF ACETYLATED HISTONES AND INDUCES CELL CYCLE ARREST AND/OR APOPTOSIS OF SOME TRANSFORMED CELLS. THE MECHANISM OF THE ANTINEOPLASTIC EFFECT OF VORINOSTAT HAS NOT BEEN FULLY CHARACTERIZED.