Auranofin lightgray 300x3003-D structure of  the Auranofin molecule with a gold atom in dark-yellow bound between the light-yellow sulfur and orange phosphorus.

Amebiasis research within the CDIPD is focused on developing drug discovery strategies and identifying novel pharmaceutics for the treatment of this diarrheal disease. Our drug discovery research for amebiasis uses a two-pronged approach, combining a strategy of repurposing compounds that are already in clinical development along with the development of compounds with novel scaffolds and improved activity against the parasite. In addition, our research focuses on the identification of key transcriptional changes as well as the role of proteases in influencing the behavior of pathogenic amebae.  

We are also interested in developing innovative technologies for pharmaceutical sciences research and we have developed state-of-the-art technologies to prosecute small molecule discovery in a more rigorous and multidimensional capacity. 

  • Our research addressed a major question in amebiasis research: why are some organisms capable of producing severe invasive disease whereas others are nonpathogenic? 
  • We developed shotgun genomic microarray for Entamoeba histolytica. As a complement to microarray analysis, we also applied specific biochemical tools to the study of a cluster of protease genes identified in the pathogen that were hypothesized to play a role in pathogenesis. 
  • An important finding from our research is that the bacterial biofilm of the colon, mucins produced by intestinal epithelial cells, and sugars like N-acetylgalactosamine (GalNAc) are all key elements in determining whether amebae will express a “commensal” phenotype, or release virulence factors. 
  • We developed an automated high-throughput screening (HTS) methodology for the E. histolytica viability assay. 
  • Our HTS methodology discovered the amebicidal activity of an FDA-approved oral drug, auranofin. 
  • Drug repurposing led to an FDA orphan drug status of auranofin for the treatment of amebiasis. 
  • Auranofin, with support from the National Institutes of Health (NIH), completed Phase 2 clinical trial for amebiasis. 

Our studies are providing important new clues about how a pathogen orchestrates responses to the host environment. The knowledge generated in these studies will help generate new types of therapeutics for the treatment of amebiasis and other amebic infections. 

 

 

pipeline 720x38
  • Cysteine proteases and other targets arise from screening activities
  • Thioredoxin reductase
  • Compound libraries from various sources
  • FDA-approved compounds
  • Auranofin
  • Cysteine protease inhibitors
  • Hsp90 inhibitors
  • Kinase-targeted inhibitors
  • Auranofin IND-enabling
  • Orphan Drug Status of Auranofin from the FDA

Amebiasis Publications