Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections

Parasitology. 2014 Jan;141(1):140-6. doi: 10.1017/S003118201300142X. Epub 2013 Aug 28.

Abstract

The Drugs for Neglected Diseases initiative (DNDi) has defined and implemented an early discovery strategy over the last few years, in fitting with its virtual R&D business model. This strategy relies on a medium- to high-throughput phenotypic assay platform to expedite the screening of compound libraries accessed through its collaborations with partners from the pharmaceutical industry. We review the pragmatic approaches used to select compound libraries for screening against kinetoplastids, taking into account screening capacity. The advantages, limitations and current achievements in identifying new quality series for further development into preclinical candidates are critically discussed, together with attractive new approaches currently under investigation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / pharmacology*
  • Chagas Disease / drug therapy
  • Chagas Disease / parasitology
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • High-Throughput Screening Assays
  • Humans
  • Inhibitory Concentration 50
  • Leishmania donovani / drug effects*
  • Leishmania donovani / growth & development
  • Leishmaniasis / drug therapy
  • Leishmaniasis / parasitology
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / pharmacology*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / growth & development
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / growth & development
  • Trypanosomiasis, African / drug therapy
  • Trypanosomiasis, African / parasitology

Substances

  • Antiprotozoal Agents
  • Small Molecule Libraries