- Target disease: Leishmaniasis
- Main partners (since project start): AbbVie, USA; Charles River, France; Centre for Drug Candidate Optimisation (CDCO), Monash University, Australia; Eurofins CEREP, France; Eurofins Pharma Discovery Services (formerly Eurofins Panlabs), USA; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; London School of Hygiene & Tropical Medicine, UK; Pfizer, USA; Sandexis, UK; Takeda Pharmaceutical Company Ltd., Japan; WuXi AppTech, China.
- Project start: February 2012
- Funding (since project start): Department for International Development (DFID), UK; Global Health Innovative Technology (GHIT) Fund, Japan.
The aminopyrazole class of compounds originally from Pfizer has shown promising early profiles for the treatment of both visceral leishmaniasis 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, pharmacokinetics, and initial in vitro safety assays are all underway. The ongoing lead optimization programme in collaboration with Takeda and supported by the GHIT Fund aims to select an optimized lead.
While a pre-clinical trial application studies package composed of toxicology and safety studies should start in early 2019 for the lead compound DNDI-5561, further work on the back-ups from this series is currently on hold. However, new chemical spaces continue to be investigated through the Open Synthesis Network, a collaborative project that engages master’s and undergraduate students in research for neglected diseases.
DNDI-5561 was nominated as a new pre-clinical candidate from the aminopyrazole series in October 2017. Four back-up compounds are well advanced and offer similar profiles to DNDI-5561. Additional studies, including preliminary toxicology assessments, are being planned to further understand the safety profiles of these compounds and to identify the best back-up to DNDI-5561.
Last update: February 2019