Identification of lead compounds for Leishmania donovani and/or Trypanosoma cruzi
  • Awarded Year
    2016
  • Awarded Amount
    $780,000
  • Disease
    NTDs
  • Intervention
    Drug
  • Development Stage
    Lead Identification
  • Collaboration Partners
    Daiichi Sankyo, Inc., Drugs for Neglected Diseases initiative

Introduction and Background of the Project

Introduction

Daiichi-Sankyo and DNDi jointly carried out a high throughput screening (HTS) of 40,000 compounds of the Pharamscape collection against Leishmania donovani and/or T. cruzi at Institut Pasteur Korea. A total of around 50 chemotypes were identified from primary active compounds followed in dose-response confirmation measurements. Three active chemotypes and 2 back-ups were prioritized in order to be progressed into Hit to Lead.

 

Project objective

The objective of the project is to identify at least 1 -possibly 2 or more – progressable lead series meeting DNDi lead stage criteria for visceral leishmaniasis and/or Chagas disease

 

Project design

The design of the Pharmaspace collection and of the medicinal chemistry program associated with this Hit-to-Lead program has been made by Daiichi Sankyo. The design of the test cascade related to the biological (parasitology) assesssement of the active series selected for this project has been established by DNDi. 

How can your partnership (project) address global health challenges?

Drug discovery and development at the early hit to lead stage for visceral leishmaniasis and Chagas disease is prone to a relatively high chance of failures. A critical mass of novel chemical series therefore needs to be identified and progressed through H2L and beyond in order to build up a solid portofolio of preclinical candidates aligned with the DNDi TPPs for those 2 kinetoplastid diseases.

 

What sort of innovation are you bringing in your project?

 

Daiichi Sankyo and DNDi have ensured through structure-based assessment that all active series included in this proposal do not have any overlap with past and current DNDi H2L/LO programs as well as scientific literature for VL and Chagas.

Role and Responsibility of Each Partner

Daiichi Sankyo will have the responsibility of the Design, synthesis of the compounds to be generate in the course of this project. Daiichi Sankyo will additionnaly be in charge of the assays related to the assessment of the physicochemical properties and DMPK of those compounds. The in vitro and in vivo parasitology assays (Leishmanial donovani and anti-T. cruzi) will be run at DNDi in collaboration with its mandated screening centers. Institut Pasteur Korea acting as the primary screening center in the frame of this Hit-to-Lead collaboration project.