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Vincent, Fabien; Loria, Paula M.; Weston, Andrea D.; Steppan, Claire M.; Doyonnas, Regis; Wang, Yue-Ming; Rockwell, Kristin L.; Peakman, Marie-Claire
Cell chemical biology, 11/2020, Letnik: 27, Številka: 11Journal Article
The promise of phenotypic screening resides in its track record of novel biology and first-in-class therapies. However, challenges stemming from major differences between target-based and phenotypic screening do exist. These challenges prompted us to rethink the critical stage of hit triage and validation on the road to clinical candidates and novel drug targets. Whereas this process is usually straightforward for target screening hits, phenotypic screening hits act through a variety of mostly unknown mechanisms within a large and poorly understood biological space. Our analysis suggests successful hit triage and validation is enabled by three types of biological knowledge—known mechanisms, disease biology, and safety—while structure-based hit triage may be counterproductive. Display omitted Phenotypic and target screening have important differences. Vincent et al. conduct an analysis of the hit triage process for phenotypic screens, which suggests successful hit validation and prioritization is best enabled by three types of biological knowledge—known mechanisms, disease biology, and safety—while structure-based hit triage may be counterproductive.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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