title: Dual-specificity phosphatases as molecular targets for inhibition in human disease.
abstract: CONCLUSIONS
  The dual-specificity phosphatases (DUSPs) constitute a heterogeneous group of cysteine-based protein tyrosine phosphatases, whose members exert a pivotal role in cell physiology by dephosphorylation of phosphoserine, phosphothreonine, and phosphotyrosine residues from proteins, as well as other non-proteinaceous substrates.
  
  
  BACKGROUND
  A picture is emerging in which a selected group of DUSP enzymes display overexpression or hyperactivity that is associated with human disease, especially human cancer, making feasible targeted therapy approaches based on their inhibition. A panoply of molecular and functional studies on DUSPs have been performed in the previous years, and drug-discovery efforts are ongoing to develop specific and efficient DUSP enzyme inhibitors. This review summarizes the current status on inhibitory compounds targeting DUSPs that belong to the MAP kinase phosphatases-, small-sized atypical-, and phosphatases of regenerating liver subfamilies, whose inhibition could be beneficial for the prevention or mitigation of human disease.
  
  
  RESULTS
  Achieving specificity, potency, and bioavailability are the major challenges in the discovery of DUSP inhibitors for the clinics. Clinical validation of compounds or alternative inhibitory strategies of DUSP inhibition has yet to come.
  
  
  CONCLUSIONS
  Further work is required to understand the dual role of many DUSPs in human cancer, their function-structure properties, and to identify their physiologic substrates. This will help in the implementation of therapies based on DUSPs inhibition.
authors.affiliation: 1 Genome Biology Unit, European Molecular Biology Laboratory , Heidelberg, Germany .
authors.forename: Pablo
authors.initials: P
authors.lastname: Ríos
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Nunes-Xavier
authors.forename: Lydia
authors.initials: L
authors.lastname: Tabernero
authors.forename: Maja
authors.initials: M
authors.lastname: Köhn
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
mesh_terms: D000595:Amino Acid Sequence; D054637:Dual-Specificity Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D054637:Dual-Specificity Phosphatases