Chagas Translation

 

  • Target disease: Chagas
  • Main partners (since project start): AbbVie, USA; AstraZeneca, UK; Brazilian Biosciences National Laboratory, Brazil; Centre for Drug Candidate Optimization, Monash University, Australia; Drug Discovery Unit, University of Dundee, UK; Epichem, Australia; Eisai Co Ltd, Japan; Eskitis Institute for Cell and Molecular Therapies, Griffith Institute for Drug Discovery, Australia; Fundaçao de Apoio Universidade Federale de Sao Paolo, Brazil; GlaxoSmithKline, UK; Griffith University, Australia; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; Institut Pasteur Korea, South Korea; London School of Hygiene & Tropical Medicine, UK; Merck, USA; Shionogi & Co Ltd, Japan; Sanofi, France; Sandexis, UK; Takeda Pharmaceutical Company Ltd, Japan; The Swiss Tropical and Public Health Institute, Switzerland; TCG Life Sciences, India; University of Campinas, Brazil; Universidad Sao Paolo, Sao Carlos, Brazil; WuXi AppTech, China.
  • Project start: Ongoing
  • Funding (since project start): Department for International Development (DFID), UK; Médecins Sans Frontières/Doctors without Borders, International; Australian Research Council (ARC), Australia; Ministry of Health, Brazil.

 

Overall Objective:

  • Identify new leads series from current ongoing Hit-to-Lead activities by taking advantage of the optimization consortia and screening platforms for Chagas disease.

 

Multiple hits from screening with several pharmaceutical partners or from other sources have been progressed into hit confirmation and expansion studies. Several promising series, issued from the published hit list from “GSK Kinetoplastid Boxes” and Celgene, have been identified and are currently moving into the Hit-to-Lead stage; one series showed Proof of Principle in vivo and is in Lead Optimization. In order to identify hit series with a different mechanism of action, the screening cascade has been modified to filter out potential CYP51 inhibitors (same mechanism of action as posaconazole or ravuconazole), and prioritizing trypanocidal compounds early on. The insights gained from additional in vitro assays, coupled with a new in vivo model based on bioluminescent imaging, was developed at the LSHTM. The model predicts the outcome of benznidazole and posaconazole in clinical trials, enabling compounds to be moved forward with more confidence.

Opportunities for new candidates to include in the pipeline are continually under review. Preliminary mapping and set-up of discovery activities are continuing in Latin America in accordance with the global DNDi strategy of empowerment of, and funding from, the regional offices.


Last update: August 2017