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The goal of this paper is to review the variety of approaches used to improve lead generation, in terms of cost, time and risk management. Our analysis shows that successful lead generation requires not only an accurate definition of the needs (to define the most relevant assay protocols and readouts), but most of all a good hit as a starting point. It also appears that teams where techniques and knowledge are combined, are more successful in that difficult game.
Keywords: Hit-to-lead (H2L), optimisation, High Throughput Screening (HTS), parallel synthesis, library design, Structure-activity relationships (SAR), Structure-property relationships (SPR), functional assay, druggability, rational drug design
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