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Abstract

Mass receptor screening is capable of identifying drug candidates in large compound libraries. Our laboratory has developed a mass screening technology by standardizing assay protocols that can be transferred from receptor to receptor. The entire operation, from disbursement of compounds to data analysis, is computerized to handle vast numbers of experimental results. The success of this method depends upon strict definitions of compound activity, with rapid elimination of compounds that do not fulfill all criteria. Finally, we approach automation with caution. While certain items, such as automatic harvesters, are essential for high-throughput screening, much time can be spent optimizing gadgets instead of gathering data.

Biophysical methods in early drug discovery

“…Alongside this, existing biophysical approaches were used in novel ways to identify and characterise protein-ligand interactions, for example the first report of the use of affinity selection, coupled to detection by mass spectrometry, for the identification of molecules binding to a macromolecule [ 3 ], and the use of nuclear magnetic resonance (NMR) to identify fragments that could subsequently be optimised and linked to form more potent compounds [ 4 ]. The development of these biophysical methods coincided with the advent of high-throughput screening (HTS), leading from natural product screening of a few hundred compounds each week in the late 1980s, through to HTS hits being responsible for starting matter for almost half of drug companies’ portfolios in the mid-1990s [ 5 , 6 ]. This allowed the valuable combination of biophysics with HTS to contribute to the establishment of high quality, high-throughput assays through the characterisation of protein and tool ligands, as well as the evaluation of HTS output through orthogonal application of biophysical methods to screen for true target engagement [ 7 ].…”