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• W98992460 abstract "During the past decade high-throughput screening (HTS) has established itself as a core technology within the pharmaceutical industry. Its characteristic feature is the combination of sophisticated laboratory automation with economical and miniaturized assay technology, aiming at rapid and efficient screening processes. Automated screening equipment has reached a high level of maturity and can be used in seemingly endless combinations from different sources to provide solutions for almost any requirement in the in vitro steps of the drug discovery process. In parallel, a wide variety of biochemical and cellular assay technologies have been developed and are used to efficiently screen large compound libraries. Today the industry realizes that even huge compound collections are no more than a spoonful out of the ocean of chemical space and, therefore, rational concepts need to be employed for their best composition. An additional prerequisite for a successful drug discovery process is the choice of the appropriate targets. The sequencing of the human genome has fueled the imagination about a rich supply of novel targets. However, recent thinking on the druggability of targets considers that only a fraction of them may be accessible by small molecules. This limitation will impact on target selection and screening strategies. Despite the fact that novel screening technologies are evolving at a high rate screeners have experienced significant numbers of non target-related effects within their assays, which create noise in screening results. As a consequence, screening laboratories are developing strategies to confirm primary data by orthogonal tests using alternative assays and implementing secondary screening within their processes for fast confirmation of hits. Additionally, many companies are establishing a post screening hit-to-lead process aiming at a rigorous selection of most promising hit classes including considerations beyond the primary target potency. In parallel, there is a constant development of novel, more reliable screening technologies. One such innovative approach is the screening for phenotypic events within cells, widely referred to as high-content screening (HCS). HCS can be defined as automated microscopy or efficient interrogation of cellular systems with high resolution using multiparametric readouts. Since the introduction of the first systems at the end of the last century, a broad range of instruments with different and improved capabilities have entered the market. Simultaneously, various assay technologies have been developed and are becoming commercially available. Due to throughput limitations automated microscopy has initially been used in secondary screening but, recent technical improvements now also allowing its application in primary screening. Pioneering groups in the field using different concepts based on phenotypic cellular observations are already advancing compounds from HCS as first development candidates. HCS will be discussed in the context of an evolution of screening approaches towards more efficiency in finding biologically relevant lead structures and finally better drugs." @default.
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• W98992460 date "2007-01-01" @default.
• W98992460 modified "2023-09-25" @default.
• W98992460 title "High-Throughput and High-Content Screening" @default.
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• W98992460 doi "https://doi.org/10.1016/b0-08-045044-x/00105-x" @default.
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