Drug Discovery: Enabling both Target-based and Phenotypic Assays
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The pursuit of the human genome project in the 1990s led to an explosion of genomic data and putative drug targets based on sequence homology to targets of known drugs. This led drug discovery efforts to adopt almost exclusively a hypothesis-driven, target-based approach, largely at the expense of classical pharmacology approaches that relied on functional (phenotypic) assays linked to the disease, with no a priori knowledge of the mechanism of action . The target-based approach vastly simplified assay development for screening purposes relative to classical pharmacology due to the ability to purify or create recombinant drug targets, which enabled rapid compound screening for binding activity. This resulted in the development of automated, industrialized methods that enabled rapid screening of enormous libraries of small molecule compounds, often in excess of millions of chemical compounds .
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