Final Report

1. Project objective

The objective of the project was to identify novel antimalarials from a ~20,000 compound Takeda library (compounds not previously screened for antimalarial activity). The hit compounds identified should meet MMV and GHIT criteria for progression to the hit-to-lead phase.

2. Project design

Takeda (Osaka, Japan) assembled a 20k diverse set of compounds filtered by 200

3. Results, lessons learned

111 hit compounds were identified from the phenotypic high-throughput screening. Hit confirmation (concentration-response) allowed identification of 43 compounds with potency against drug sensitive strain (Pf3D7) < 2 μM and SI >50 (24 compounds with Pf3D7 IC50 < 1 μM). 7 hit series were prioritized based on potency, structural novelty and chemical attractiveness. The selected hit series were further profiled (cross-resistance assays to remove unwanted mode of actions, in vitro killing rate, ADMET). The project team is currently reviewing the data and will decide whether 2-3 hit series are suitable for a GHIT HTLP proposal.