title: Emerging approaches for histone deacetylase inhibitor drug discovery.
abstract: BACKGROUND
  Histone deacetylases (HDACs) are key players in the mediation of gene expression for both cancerous and noncancerous malignancies. Overexpression of these enzymes has been demonstrated in numerous types of cancer with some enzyme isoforms also involved in neurological, inflammatory and viral pathologies. Hence, the development of HDAC inhibitors (HDACis) represents a promising approach for their treatment. Numerous chemical entities have been studied in the recent years and some of them have reached clinical trials.
  
  
  METHODS
  This review summarizes the recent efforts in the drug development of HDACis and their potential application as therapeutic agents in cancerous, neurological, inflammatory and viral diseases.
  
  
  CONCLUSIONS
  The development of novel potent and selective HDACis is ongoing. However, increased scientific effort is needed to aid the fight of specific types of cancerous or noncancerous disease with more selective agents required to avoid side effects during therapy. An interesting therapeutic approach is the use of HDACis in combination with other epigenetic target modulators to combine their therapeutic potential for a synergistic effect.
authors.affiliation: Sapienza University of Rome, Department of Drug Chemistry and Technologies , Piazzale Aldo Moro 5, 00185 Rome , Italy +00390649913392 ; sergio.valente@uniroma1.it ; antonello.mai@uniroma1.it.
authors.forename: Clemens
authors.initials: C
authors.lastname: Zwergel
authors.forename: Sergio
authors.initials: S
authors.lastname: Valente
authors.forename: Claus
authors.initials: C
authors.lastname: Jacob
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: cancer; epigenetics; histone deacetylases; inhibitors; neurology; small molecules; viral infections