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

The process of hit-to-lead optimization is ongoing, with multiple series being progressed based on outputs of the screening programme. A variety of hit-to-lead mechanisms and exploration strategies are being used to progress towards in vivo proof-of-concept studies in pre-clinical efficacy models of Chagas disease.

The NTD Drug Discovery Booster is a related project conducting early-stage drug discovery to identify new treatments for leishmaniasis and Chagas disease.

Project updates

2020

Approximately 15 distinct series from various origins were progressed.

2019

DNDi has continued its efforts in screening chemically diverse libraries to replenish the discovery pipeline. Confirmed new hits are continuously feeding the hit-to-lead pipeline. In 2019, a new consortium was established in collaboration with University of Campinas and University of Sao Paulo in Brazil. Through a team of scientists working in a global network, PITE (Research Partnership for Technological Innovation) aims to deliver a high-quality pre-clinical candidate compound that could become a new treatment for Chagas disease.

2018

DNDi has continued its efforts in screening chemically diverse libraries for identification and confirmation of new hits that could progress and feed the hit-to-lead pipeline. In 2018, a new partnership was established with the Drug Discovery Unit from Dundee University in Scotland and GSK to jointly characterize and progress new promising hits.

2017

A new discovery cascade has been implemented comprising new in vitro and in vivo. If promising activity is demonstrated, the identified series would then be advanced into full lead optimization programmes.