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• W2045790762 abstract "Antimalarial drug discovery has historically benefited from the whole-cell (phenotypic) screening approach to identify lead molecules in the search for new drugs. However over the past two decades there has been a shift in the pharmaceutical industry to move away from whole-cell screening to target-based approaches. As part of a Wellcome Trust and Medicines for Malaria Venture (MMV) funded consortium to discover new blood-stage antimalarials, we used both approaches to identify new antimalarial chemotypes, two of which have progressed beyond the lead optimization phase and display excellent in vivo efficacy in mice. These two advanced series were identified through a cell-based optimization devoid of target information and in this review we summarize the advantages of this approach versus a target-based optimization. Although the each lead optimization required slightly different medicinal chemistry strategies, we observed some common issues across the different the scaffolds which could be applied to other cell based lead optimization programs." @default.
• W2045790762 created "2016-06-24" @default.
• W2045790762 creator A5036011732 @default.
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• W2045790762 date "2012-03-01" @default.
• W2045790762 modified "2023-09-30" @default.
• W2045790762 title "Back to the Future: Lessons Learned in Modern Target-based and Whole-Cell Lead Optimization of Antimalarials" @default.
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• W2045790762 doi "https://doi.org/10.2174/156802612799362977" @default.
• W2045790762 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3355380" @default.
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