title: Whole-organism high-throughput screening against Trypanosoma brucei brucei.
abstract: BACKGROUND
  Human African trypanosomiasis (HAT) occurs as a result of infection with the protozoan parasites Trypanosoma brucei gambiense and T.b. rhodesiense and is nearly always fatal without treatment. However, current therapeutic options are severely limited and there is a desperate need for new compounds to treat the disease. Whole-cell high-throughput screening (HTS) is a technique frequently used to identify compounds with trypanocidal activity.
  
  
  METHODS
  The authors examine the development of whole-organism HTS assays for T.b. brucei. The authors describe the successes achieved through HTS and discuss the advantages and disadvantages of whole-organism HTS.
  
  
  CONCLUSIONS
  Despite hundreds of trypanocidal molecules being identified by whole-organism HTS, very few have progressed into preclinical development. The failure of molecules identified by HTS to progress along the drug development pathway is due to a multitude of factors including undrug-like molecules and molecules having poor pharmacodynamics/kinetic properties. Future studies should focus on screening libraries that contain drug-like molecules that possess some of the properties required in the final compound.
authors.affiliation: Discovery Biology, Eskitis Institute (N27), Griffith University, Brisbane, 4111, Australia.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Jones
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
mesh_terms: D000818:Animals; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D006801:Humans; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000453:epidemiology
chemical_list: D014344:Trypanocidal Agents