title: Recent advances in proteasome inhibitor discovery.
abstract: BACKGROUND
  Proteasome inhibition is a quickly advancing subject of research and has a significant potential to become a potent therapeutic modality for many diseases and disorders. The aim of this review is to present the reader with the variety of approaches to the proteasome inhibitor discovery as well as highlight the diversity of scaffolds being considered for this task.
  
  
  METHODS
  This review focuses on current developments in proteasome inhibitor discovery, including an account of research efforts covered in the literature from the years 2009 - 2012, although some of the earlier work is also mentioned. Specifically, presented are the type of experiments performed, the compounds and compound families investigated along with their activities and assessment for potential therapeutic value. In particular, authors highlight different paths to discovery of the proteasome inhibitors such as screening of large libraries, repurposing of existing therapeutics, development of compounds with known proteasome inhibitory activities as well as utilizing novel scaffolds.
  
  
  CONCLUSIONS
  Discovery of therapeutically successful proteasome inhibitors depends on a number of factors and demands a multipronged approach. Screening protocols, choice of assays, desired mode of action, selection of a binding pocket, targeting and delivery strategy, all require careful consideration when attempting to target the proteasome.
authors.affiliation: University of South Florida, Chemistry, 4202 E Fowler Ave, Tampa, FL 33612, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pevzner
authors.forename: Rainer
authors.initials: R
authors.lastname: Metcalf
authors.forename: Melanie
authors.initials: M
authors.lastname: Kantor
authors.forename: Desiree
authors.initials: D
authors.lastname: Sagaro
authors.forename: Kenyon
authors.initials: K
authors.lastname: Daniel
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054852:Small Molecule Libraries
chemical_list: D061988:Proteasome Inhibitors; D054852:Small Molecule Libraries