Drug (lead) discovery relies on massive screening of chemical libraries against various extra- and intracellular molecular targets to find compounds with the desired mode of action. Sequencing of the human genome1 has generated a large number (>40 per cent) of new molecular targets with unknown function (‘orphan targets’), as well as a large number of molecular targets with known function albeit non-tractable by standard high-throughput screening (HTS) due to the particular requirements of plate-based assays in robotic screening systems (‘non-tractable targets’). Examples of the latter are targets with very fast kinetics, targets with multiple modes of function for the same polypeptide chain or targets where the substrate of a particular enzyme is not known.
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