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Affinity-based screening techniques: Their impact and benefit to increase the number of high quality leads

Bergsdorf, Christian and Ottl, Johannes (2010) Affinity-based screening techniques: Their impact and benefit to increase the number of high quality leads. Expert Opinion on Drug Discovery, 5 (11). pp. 1095-1107. ISSN 1746-045X


The generation of new chemical leads as a starting point for drug development is the first critical step in the drug discovery process after target identification and validation. Since the beginning of 90s high-throughput screening (HTS) has rapidly evolved to one of the main sources for new chemical entities by testing large compound libraries for activity against a target of interest in biochemical in vitro tests using the recombinant protein or cell-based assays. Since the last recent years traditional functional assay read-out technologies using labeled detection reagents are complemented by biophysical methods which directly measure the physical interaction (affinity) between a low molecular weight compound and a target protein in a completely label-free mode. Affinity-based methods offer the opportunities (i) to address non-tractable targets e.g. orphan receptors or functionally inactive protein forms, (ii) to screen extremely large compound files (> 10 mil.) e.g. DNA-encoded libraries and (iii) to characterize HTS hits with an orthogonal assay read out enabling to sort out HTS assay artefacts and to prioritize compounds. This review will focus on the principle, application and impact of selected affinity-based technologies in (i) primary screening for hit identification and (ii) hit validation and qualification to select the most promising chemotypes for further investigation. We will highlight how throughput, robustness and information content of affinity-based methods guide and determine their efficient best value use in the different phases of lead finding.

Item Type: Article
Additional Information: author can archive post-print (ie final draft post-refereeing) Restrictions: 12 month embargo for STM, Behavioural Science and Public Health Journals 18 month embargo for SSH journals
Keywords: affinity-based, label-free, biophysics, high-throughput screening, binding
Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16


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