Leishmaniasis Research

 

  • Target disease: VL
  • Main partners (since project start): Takeda Pharmaceutical Company Ltd, Japan; WuXi AppTech, China; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; London School of Hygiene and Tropical Medicine, UK; Pfizer, UK; Sandexis, UK.
  • Project start: February 2012
  • Funding (since project start): Department for International Development (DFID), UK; Global Health Innovative Technology (GHIT) Fund, Japan.

 

Overall Objective: 

  • Select a pre‑clinical candidate from the aminopyrazole series for the treatment of VL.

 

Compound mining of well-annotated chemical compound libraries has been used to identify a new class of compounds active against VL. In June 2014, the first in vivo proof of concept for VL series 12 (aminopyrazoles) from Pfizer was achieved in the hamster early curative model of VL. An initial compound gave 93% and 95% reductions in parasitaemia in liver and spleen respectively after five days oral dosing at 50mg/kg BID, with a subsequent compound showing even better in vivo activity (>99% reduction in parasitaemia in both liver and spleen).

The aminopyrazole class of compounds has shown promising early profiles for the treatment of both visceral and cutaneous leishmaniasis. Profiling of current and new leads in a panel of drug-sensitive and drug-resistant strains of leishmania, exploration of the in vivo dose response, rat pharmacokinetics, and initial in vitro safety assays are all underway. The ongoing lead optimization programme aims to select an optimized lead.
The project moved into the lead optimization stage in January 2015, with GHIT Fund support and expert scientific assistance from Takeda from April 2015.

 

Last update: February 2017