Histone Deacetylase Complexed with Vorinostat

Histone deacetylases (HDACs) are a class of enzymes used to remove acetyl groups from an ε-N-acetyl-lysine amino acid on a histone, allowing for the tighter wrapping of DNA. This is associated with less DNA transcription, thus HDACs are crucial for controling gene expression. Dysregulation of HDAC activity contributes severe implications including cancers, cardiovascular or neurological diseases. Vorinostat is a HDAC inhibitor (HDACi) in the hydroxamate group. It is associated as an emergency class of drugs due to its potential anti-neoplastic activity regarding its use as a chemotherapy drug which may have detrimental side effects including nausea, vomiting and suppression of bone marrow function. Other drugs used for HDACi are benzamide containing inhibitors, however these are slow and tight-binding with long residence times. HDACi with increased isozyme selectivity and potency may broaden their clinical utility and minimize side effects. This tour elucidates the fast acting mechanisms of vorinostat.