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High-throughput screening (HTS) of libraries of up to 106 compounds aims to find inhibitors for therapeutic targets using rapid assays, often via a yes/no readout.
However, there is a high frequency of false-positives from primary HTS assays and few hits become lead compounds. Introducing higher quality analysis techniques into the screening workflow after the first round of hits help you to confidently select the most relevant compounds.
Functional assays in early drug discovery help you to better understand the mechanism of action and provide predictive data for efficacy and safety. Phenotypic assays are an excellent complement to the more target-based screening approach.
Biacore systems measure real-time binding of unmodified biomolecules and are often used for development and troubleshooting of screening assays for hit identification. Binding characteristics of pairs in a sandwich or competitive assay allow for affinity optimization, providing a robust screening assay with low background and low replicate variability. Characterization of assay performance under varying conditions helps optimize the protocol further.
Biacore binding assays are well-established for fragment-based hit identification. With sensitive label-free detection and an innate ability to detect weak interactions for very small compounds (<250 Da), Biacore assays provide both affinity and selectivity data within the same screen.
HCA is increasingly used to complement HTS. Our IN Cell Analyzer systems and cell-based assays for high-content cell imaging and analysis can provide valuable insights into the mechanism of action and toxic effects of drug compounds in a relevant biological context. IN Cell Analyzer systems allow the observation and quantitation of multiple biological parameters within living and fixed cells, complementing data obtained from biochemical/biophysical assays.
Surface plasmon resonance (SPR) label-free technology facilitates detailed study of how lead compounds and antibodies bind to drug targets.
High-content analysis (HCA) gives deeper insights into how a drug or compound acts in a functional context providing for more information and confidence in both hit selection and safety and efficacy.
Biomolecular imagers for sensitive and quantitative digital imaging.
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