Our African Sleeping Sickness Research

The CDIPD has had a long-standing interest in the biological function of the trypanosome proteases and we continue to explore proteases as a potential target class as well as to gain better understanding of key trypanosome pathways.

In collaboration with Jack Taunton's laboratory at UCSF, we have also been probing the biology of several Trypanosoma brucei kinases. Through these efforts we have identified several possible drug targets. We are currently focusing on screening of these kinases, as well as whole parasite screening of kinase inhibitor libraries.

We continue to do a significant amount of whole parasite screening to identify compounds that may be relevant hits for lead development. Compounds with anti-trypansomal activity may also be useful tools to explore parasite biology and identify new targets and pathways of interest. Some of our collaborations in this area include a collaboration in natural products chemistry with Roger Linington at UCSC. This collaboration has continued to identify compounds that may become promising tools and leads. We also are collaborating with researchers at Stanford to test FDA approved compounds for activity against T. brucei with the goal of repurposing for use in treatment of this disease. Finally, we continue to have numerous small collaborations, such as those with Pharmadyn testing focused compound libraries against T. brucei to identify possible new lead series to pursue in our drug development efforts.

Trypanosoma brucei (BS stumpy form on millipore filter)
Trypanosoma brucei (BS stumpy form on millipore filter). Credit: WHO/TDR/Vickerman
Photomicrograph of Trypanosoma brucei
Photomicrograph of Trypanosoma brucei gambienese. Credit: WHO/TDR

African Sleeping Sickness Research Progress

Target Discovery

  • Proteases
  • Kinases
  • Utilizing tool anti-trypanosomal compounds to explore potential targets and pathways

Screening

  • Targeting whole parasite:
    1. Stanford/FDA approved compounds
    2. Natural Products – Phil Crews and Roger Linington/UCSC
  • Kinase targeted libraries
  • Screening of novel kinase targets

Lead Validation / Lead Optimization

  • Novel kinase target hit-to-lead chemistry

Pre-Clinical

African Sleeping Sickness Publications