Designing selective inhibitors for calcium-dependent protein kinases in apicomplexans

Raymond Hui, Majida El Bakkouri, L. David Sibley

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

Apicomplexan parasites cause some of the most severe human diseases, including malaria (caused by Plasmodium), toxoplasmosis, and cryptosporidiosis. Treatments are limited by the lack of effective drugs and development of resistance to available agents. By exploiting novel features of protein kinases in these parasites, it may be possible to develop new treatments. We summarize here recent advances in identifying small molecule inhibitors against a novel family of plant-like, calcium-dependent kinases that are uniquely expanded in apicomplexan parasites. Analysis of the 3D structure, activation mechanism, and sensitivity to small molecules had identified several attractive chemical scaffolds that are potent and selective inhibitors of these parasite kinases. Further optimization of these leads may yield promising new drugs for treatment of these parasitic infections.

Original languageEnglish
Pages (from-to)452-460
Number of pages9
JournalTrends in Pharmacological Sciences
Volume36
Issue number7
DOIs
StatePublished - Jun 26 2015

Keywords

  • ATP-binding pocket
  • chemotherapy
  • gatekeeper
  • orthogonal inhibitors
  • parasites
  • serine-threonine protein kinases

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