The Handbook of Medicinal Chemistry
Chapter 10: Assays1
Published:03 Feb 2023
Barbara Saxty, Peter J. Coombs, 2023. "Assays1", The Handbook of Medicinal Chemistry, Simon E Ward, Andrew Davis
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Identification of a disease-relevant target is the first step in drug discovery. The target and disease are then central to the design of a series of assays (assay cascade) against which compounds can be assessed for progression through the drug discovery process. Given the desired outputs and known variables, the principles of assay design and development are relatively simple. They are to build an assay that reliably estimates the activity of compounds whilst retaining a link to the disease biology and to have this assay run as often as is required to enable quick decision making. Project assay cascades typically begin with simple biochemical tests. As compounds are developed, the assays become more physiologically relevant and pharmacologically predictive. When data divergence becomes apparent, the use of orthogonal assays, even if in themselves they are not better than the primary read out, can offer the researcher insights into the mechanism of action for the selection of the best series to progress. This chapter gives an overview of commonly used assay formats in drug discovery cascades, highlighting their strengths and weaknesses and where they might be most effectively used.