Leishmaniasis Research

 

  • Target disease: VL
  • Main partners (since project start): Epichem, Australia; Fundaçao de Apoio Universidade Federale de Sao Paolo, Brazil; Centre for Drug Candidate Optimization, Monash University, Australia; TCG Lifesciences, India; Sandexis, UK; WuXi AppTech, China; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; London School of Hygiene and Tropical Medicine, UK; Griffith University, Australia; GlaxoSmithKline, Tres Cantos, Spain; Sanofi, France; Anacor Pharmaceuticals Inc., USA; Merck, USA; AstraZeneca, UK; AbbVie, USA.
  • 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 limited optimization to identify promising lead compounds. Series from a number of different partners have shown activity against L. donovani; work on these series to bring forward suitable candidates for lead optimization is on-going.

The project continued to evaluate hits identified from high-throughput screens and to begin the process of optimizing these new chemical series. If promising activity can be demonstrated in in vivo models of leishmaniasis, the series will be advanced into full lead optimization. This process of ‘hit-to-lead’ optimization is ongoing with multiple series from several pharmaceutical companies.
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: February 2017