In contrast to genetic aberrations, epigenetic aberrations can be reversed by the use of
histone acetyltransferase (HAT),
histone deacetylase (HDAC),
SIRT, or
histone methyltransferase (HMT) inhibitors. A well-known HDACi,
suberoylanilide hydroxamic acid, has been recently approved for the treatment of
cutaneous T cell lymphoma, and a number of HDACi are in clinical trials as anticancer drugs. In addition, HDACi could be useful in
antimalarial and antifungal
therapies and can reactivate the HIV-1 expression in latent cellular reservoirs, thus suggesting the use in a combination
therapy with
highly active antiretroviral therapy. HDACi have also been reported to have anti-inflammatory effects through inhibition of
cytokines and key
transcription factors, and to ameliorate the phenotypes in animal models of
neurological disorders. HDACi can also reactivate the
gamma-globin gene for the treatment of beta-thalassaemia, and recently were shown to relieve morphological and functional effects of muscular dystrophia. Dysfunction of HAT
enzymes is also often associated with several diseases, including
cancer; thus, the HATi can represent new chemical entities for the development of new drugs. Only a few
HMTi have been described to date, but these small molecules could be a useful scaffold to discovering new highly active and
enzyme-selective compounds to develop as
therapeutics.