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 optimization to identify promising lead compounds.

Project updates

2019

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 leishmaniasis.

2018

The process of hit-to-lead optimization is ongoing, with multiple series provided by several pharmaceutical companies as well as with hits from libraries purchased from commercial vendors and screened by DNDi. If promising activity can be demonstrated in pre-clinical models of leishmaniasis, the series will be advanced into full lead optimization.

2017

The process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies and with hits from libraries purchased from commercial vendors and screened by DNDto be advanced if promising activity can be shown in pre-clinical models.

2016

The process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies and with hits from libraries purchased from commercial vendors and screened by DNDto be advanced if promising activity can be shown in pre-clinical models.

2015

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 Pharmaceutical Company Limited, 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.