LeishmaniasisResearch

 

  • Target disease: Visceral leishmaniasis
  • Main partners (since project start): AbbVie, USA; AstraZeneca, UK; Centre for Drug Candidate Optimization, Monash University, Australia; Drug Discovery Unit, University of Dundee, UK; Epichem, Australia; Griffith Institute for Drug Discovery (formerly Eskitis Institute for Cell and Molecular Therapies), Griffith University, Australia; Eisai Co Ltd, Japan; Institut Pasteur Korea, South Korea; Fundaçao de Apoio Universidade Federale de Sao Paolo, Brazil; GlaxoSmithKline, Spain; Instituto de Física, Universidade de São Paulo (USP), Brazil; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; London School of Hygiene & Tropical Medicine, UK; Merck, USA; Pfitzer (formerly Anacor Pharmaceuticals), UK; Sanofi, France; Shionogi & Co Ltd, Japan; Sandexis, UK; Takeda Pharmaceutical Company Ltd, Japan; TCG Lifesciences, India; The Swiss Tropical and Public Health Institute, Switzerland; Universidade Estadual de Campinas, UNICAMP, Brazil; WuXi AppTech, China.
  • Project start: Ongoing
  • Funding (since project start): Department for International Development (DFID), UK; Médecins Sans Frontières/Doctors without Borders, Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; Federal Ministry of Education and Research (BMBF through KfW).

 

Overall Objective:

  • Identify new leads series from current ongoing hit-to-lead activities by taking advantage of the optimization consortia platform screening of compounds for VL.

 

Hit-to-lead is a dynamic phase in the drug discovery cascade in which small molecule hits from high throughput screens are evaluated and undergo optimization to identify promising lead compounds.

 

The process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies and with hits from libraries purchased from commercial vendors and screened by DNDi to be advanced if promising activity can be shown in pre-clinical models.

This process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies.If promising activity can be demonstrated in pre-clinical models of leishmaniasis, the series will be advanced into full lead optimization.
A notable success in January 2015 was the successful advancement of the aminopyrazole series from the hit to lead stage into the next lead optimization stage. This early work has recently been published in J. Med. Chem. In addition, the NTD Drug Discovery Booster project commenced in April 2015 working with four pharmaceutical companies: Eisai, Shionogi, Takeda, and Astra Zeneca and has so far conducted hit expansion on six different hits which are being developed for leishmaniasis and Chagas disease.

A number of pharmacokinetic and pharmacodynamic studies have been conducted in animal models of VL using existing and experimental drugs to build improved PK/PD models and ameliorate the translation of new drugs from discovery into clinical studies.


Last update: August 2018