Quantifying Target Occupancy of Small Molecules Within Living Cells.
Annu Rev Biochem
; 89: 557-581, 2020 06 20.
Article
em En
| MEDLINE
| ID: mdl-32208767
ABSTRACT
The binding affinity and kinetics of target engagement are fundamental to establishing structure-activity relationships (SARs) for prospective therapeutic agents. Enhancing these binding parameters for operative targets, while minimizing binding to off-target sites, can translate to improved drug efficacy and a widened therapeutic window. Compound activity is typically assessed through modulation of an observed phenotype in cultured cells. Quantifying the corresponding binding properties under common cellular conditions can provide more meaningful interpretation of the cellular SAR analysis. Consequently, methods for assessing drug binding in living cells have advanced and are now integral to medicinal chemistry workflows. In this review, we survey key technological advancements that support quantitative assessments of target occupancy in cultured cells, emphasizing generalizable methodologies able to deliver analytical precision that heretofore required reductionist biochemical approaches.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Química Farmacêutica
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Técnicas de Sonda Molecular
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Ensaios de Triagem em Larga Escala
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Terapia de Alvo Molecular
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Corantes Fluorescentes
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article