- RFP Year2019
- Awarded Amount$41,962
- Development StageHit Identification
- Collaboration PartnersTakeda Pharmaceutical Company Limited, Medicines for Malaria Venture (MMV)
Mabrouk MT, Huang WC, Deng B, Li-Purcell N, Seffouh A, Ortega J, Ekin Atilla-Gokcumen G, Long CA, Miura K, Lovell JF. Lyophilized, antigen-bound liposomes with reduced MPLA and enhanced thermostability. Int J Pharm. 2020 Sep 2;589:119843. doi: 10.1016/j.ijpharm.2020.119843. Epub ahead of print. PMID: 32890653.
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.