chagas-Tcruzi 300x200Electron micrograph of the parasite Trypanosoma cruzi. Credit: Stephanie Hopkins & Juan Engel
 

Our research efforts have focused on both a basic biological understanding of the parasite and the disease, as well as efforts in drug discovery, including target identification, validation, screening, and lead optimization. Our most advanced program is focused on K777, an inhibitor of the cysteine protease, cruzain. We are working jointly with DNDi and the NIAID to complete IND-enabling studies for the K777-IND package.

Recent structural biology efforts have lent insight into requirements for cruzain inhibition, and our current efforts targeting cruzain are through development of backup leads to K777 and non-peptidyl inhibitors. Finally, new leads have been identified targeting CYP51, a key enzyme in the ergosterol synthetic pathway. Additional screening and chemical optimization of leads is in progress.

To expedite hit identification and lead characterization of novel anti-trypanosmal compounds, CDIPD scientists have developed a unique image-based whole-parasite screen. Several new collaborations have been initiated around this assay including an NIH funded program with the Genome Novartis Foundation focused on development of a novel clinical candidate for treatment of Chagas.

pipeline 720x38
 
  • FDA approved compounds, Stanford University
  • Novartis Genome Foundation/T. cruzi screening
  • CYP51 target-based screening
  • K777 analogs protease inhibitors
  • CYP51 inhibitors
  K777 IND-enabling

Chagas Publications