HAT inhibitors in cancer therapy

Acetylation is a posttranslational modification occurring on lysine residues of both histone and nonhistone proteins, and it plays a crucial role in several biological settings. The acetylation reaction is catalyzed by histone acetyltransferases (HATs), and the dysregulation of this enzymatic activity is implicated in many disease conditions such as cancer and inflammatory and neurological disorders. To date, despite the identification of several histone acetyltransferase inhibitors (HATi), there is still the need for more potent, selective, and metabolically stable HATi that may serve as therapeutic agents and/or chemical tools to further advance the elucidation of complex HAT biology. In this chapter, we summarize the main features of HAT enzymes and related diseases, with a particular focus on HATi, and analyze their structure–activity relationships, modes of action, and potential use as anticancer therapeutics.