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SLAS Discov ; 23(7): 697-707, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29843542

RESUMO

The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.


Assuntos
Descoberta de Drogas , Citometria de Fluxo , Ensaios de Triagem em Larga Escala , Automação Laboratorial , Plaquetas/efeitos dos fármacos , Linhagem Celular , Biologia Computacional/métodos , Análise de Dados , Descoberta de Drogas/instrumentação , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Citometria de Fluxo/instrumentação , Citometria de Fluxo/métodos , Ensaios de Triagem em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/métodos , Humanos , Hibridomas , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
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